Quantitative Susceptibility Mapping for Drug-Addicted Human Brain

Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique that can measure the magnetic susceptibility of tissues, which can reflect their iron content. QSM has been used to detect iron accumulation in cortical and subcortical brain regions. However, its application in subcortical regions such as the basal ganglia, particularly the putamen, is rare in patients with amyotrophic lateral sclerosis (ALS). We present the case of a 40-year-old male patient with ALS who underwent an MRI for QSM. We compared his QSM images with those of a control subject and performed a quantitative analysis of the magnetic susceptibility values in the putamen regions. We also reviewed the literature on previous QSM studies in ALS and summarized their methods and findings. Our QSM analysis revealed increased magnetic susceptibility values in the bilateral putamen of the ALS patient compared to controls, indicating iron overload. This finding is consistent with previous studies reporting iron dysregulation in subcortical nuclei in ALS. We also discussed the QSM processing techniques used in our study and in the literature, highlighting their advantages and limitations. This case report demonstrates the potential of QSM as a sensitive MRI biomarker for evaluating iron levels in subcortical regions of ALS patients. QSM can provide quantitative information on iron deposition patterns in both motor and extra-motor areas of ALS patients, which may help understand the pathophysiology of ALS and monitor disease progression. Further studies with larger samples are needed to validate these results and explore the clinical implications of QSM in ALS.

BackgroundCerebral microbleeds (CMBs) are small hypointense round lesions that indicate leakage of blood products from cerebral vessels damaged by β‐amyloid‐40 (Aβ) and typically are detected by T2*‐weighted and susceptibility weighted imaging (SWI) on MRI. They are indicators of cerebral small vessel diseases, especially cerebral amyloid angiopathy (CAA), affecting cortical small arteries. Quantitative susceptibility mapping (QSM) is an advanced MRI imaging technique used to quantify the magnetic susceptibility of tissues in the human body. In this study, we utilized the QSM technique to analyze venous structures at ultra‐high resolution in a cohort of patients with AD and age‐matched control subjects using 7T MRI. Our aim is to evaluate the feasibility of using ultra‐high resolution QSM at 7T MRI to find a link between small veins and CMBs in individuals with AD.MethodIn‐vivo human imaging was performed using a 7T MRI scanner and were analyzed by two neuroradiologists. CMBs were defined as hyperintense, round lesions in the QSM images. For verification, their appearance was matched on the SWI images, where CMBs are hypointense and associated with. CMBs with an immediate adjacent to a vein were assessed in the QSM images. They were defined as CMBs with small veins connection.ResultThis high‐resolution 7T neuroimaging study investigated whether a spatial relationship between small veins and CMBs could be detected in a cohort of AD patients. QSM enabled depiction of cerebral CMBs with a direct connection to a vein and their localization. Our data support the notion that CMBs relate anatomically to veins. Understanding the role of vein pathology in CAA and its role in neurodegenerative pathologies might open novel insights in the pathophysiology of AD.ConclusionA key strength of our study lies in the utilization of high‐resolution QSM at 7T MRI. High‐resolution MRI enhances the visibility of small structures, and when maintained at the same resolution, imaging at a higher field MRI increases the signal‐to‐noise ratio. QSM elevates CMB detection sensitivity while facilitating precise visualization of the brain's venous vasculature. Notably, the postprocessing algorithm ensures a high level of specificity for venous blood susceptibilities, minimizing the likelihood of measuring arterioles or slow‐flow small arteries.

Quantitative susceptibility mapping (QSM) technique had been used to measure the magnetic susceptibility of brain tissue in clinical practice. However, QSM presented echo-time (TE) dependence, and an appropriate number of echo-times (nTEs) for QSM became more important to obtain the reliable susceptibility value. The aim of the study was to explore the optimal nTEs for quantitative susceptibility mapping (QSM) measurements of basal ganglia nuclei in the healthy brain. 3D multi-echo enhanced gradient recalled echo T2 star weighted angiography (ESWAN) sequence was acquired on a 3.0T MR scanner for QSM analysis. Regions of interests (ROIs) were drawn along the margin of the head of the caudate nucleus (HCN), putamen (Pu) and globus pallidus (GP). The mean susceptibility value and standard deviation of the ROIs were derived from the pixels within each region. CV analysis demonstrated that TE6, TE8 and TE14 ESWAN sequences presented consistent lower CV value (< 1) for QSM measure of HCN, Pu and GP. ANOVA identified that susceptibility value showed no significant difference between TE6 and TE8 in HCN, Pu and GP (P > 0.05). ICC analysis demonstrated that the susceptibility value of TE6-TE8 had the highest ICC value as compared with TE6-TE14 and TE8-TE14 in HCN, Pu and GP. Combined with the timeefficiency of MRI scanning, TE6 sequence could not only provide the reliable QSM measurement but also short imaging time. The current study identified that the optimal nTEs of ESWAN were 6 TEs (2.9ms ~ 80.9ms) for QSM measurement of basal ganglia nuclei in the healthy brain.

Objective To evaluate the distribution and age-related changes of brain iron content in healthy people using MR quantitative susceptibility mapping (QSM).Methods Sixty three healthy right-handed volunteers underwent the routine MRI and SWI scan to get SWI-unfiltered phase images and magnitude images.QSM were reconstructed from the SWI-unfiltered phase images and magnitude images using SMART software.The regions of interest at the bilateral frontal white matter and nuclei (caudate nuclews,globus pallidus,putamen,substantia nigra,dorsal thalamus,red nucleus and dental nucleus) were drawn manually,and the susceptibility was measured.The linear correlation between the susceptibility and iron concentration cited from Hallgren and Sourander's post-mortem brain study was calculated.Wilcoxon test were applied to calculate the difference between the bilateral frontal white matter and bilateral nuclei.The correlation of age with susceptibility of bilateral frontal white matter and bilateral nuclei were analyzed by Spearman correlation analysis.Results The median susceptibility (extent) of frontal white matter,caudate nucleus,globus pallidus,putamen,dorsal thalamus,substantia nigra,red nucleus and dentate nucleus of 63 healthy people were-12.81 (-31.56,8.72),39.27 (22.35,75.13),93.99 (19.19,158.75),29.16 (4.11,81.53),2.91 (-27.80,27.95),83.14 (38.57,185.79),63.49 (13.83,142.09),63.30 (36.78,128.53) ppb (× 10-9),respectively.There was high consistency with Hallgren and Sourander's study (r=0.91,P＜0.05).The susceptibility of globus pallidus was the highest,followed by substantia nigra.The least susceptibility was seen in the frontal white matter.The susceptibility of right caudate nucleus,substantia nigra,red nucleus and dental nucleus was higher than that of left side (Z value was-3.18,-4.44,-3.70 and-2.64,respectively,P＜0.05).The susceptibility of bilateral globus pallidus of the male was significantly different from that of the female (Z value was-2.27 and-2.42,respectively,P＜0.05).There was positive correlation between age and the susceptibility of bilateral caudate nucleus,putamen,red nucleus and dental nucleus (r value was 0.30 to 0.49,P＜0.05).Conclusions QSM based on the SWI-unfiltered phase and magnitude images can clearly display the cerebral nuclei and evaluate the brain iron content accurately,which is consistent with the histopathological results.Iron content of bilateral caudate nucleus,putamen,red nucleus and dental nucleus increase with aging. Key words: Magnetic resonance imaging; Iron; Age factors; Brain

Multiparametric analysis based on 18F-AV133 PET/MR imaging for clinical application in Parkinson's disease.

ObjectivesBrain iron deposition and microstructural changes in brain tissue are associated with Parkinson’s disease (PD). However, the correlation between these factors in Parkinson’s disease has been little studied. This study aimed to use quantitative susceptibility mapping combined with diffusion kurtosis imaging to investigate the effects of iron deposition on microstructural tissue alterations in the brain.MethodsQuantitative susceptibility mapping and diffusion kurtosis imaging were performed on 24 patients with early PD, 13 patients with advanced PD, and 25 healthy controls. The mean values of magnetic susceptibility and diffusion kurtosis were calculated for the bilateral substantia nigra, red nucleus, putamen, globus pallidus, and caudate nucleus, and compared between the groups. Correlation analyses between the diffusion kurtosis of each nucleus and its magnetic susceptibility parameters in PD patients and healthy controls were performed.ResultsThe study found a significant increase in iron deposition in the substantia nigra, red nucleus, putamen and globus pallidus, bilaterally, in patients with PD. Mean kurtosis values were increased in the substantia nigra but decreased in the globus pallidus; axial kurtosis values were decreased in both the substantia nigra and red nucleus; radial kurtosis values were increased in the substantia nigra but showed an opposite trend in the globus pallidus and caudate nucleus. In the substantia nigra of patients with PD, magnetic susceptibility was positively correlated with mean and radial kurtosis values, and negatively correlated with axial kurtosis. None of these correlations were significantly different in the control group. In the putamen, magnetic susceptibility was positively correlated with mean, axial, and radial kurtosis only in patients with advanced-stage PD.ConclusionOur study provides new evidence for brain iron content and microstructural alterations in patients with PD. Iron deposition may be a common mechanism for microstructural alterations in the substantia nigra and putamen of patients with PD. Tracking the dynamic changes in iron content and microstructure throughout the course of PD will help us to better understand the dynamics of iron metabolism and microstructural alterations in the pathogenesis of PD and to develop new approaches to monitor and treat PD.

Voxel-based morphometry (VBM) is widely used to quantify the progression of Alzheimer's disease (AD), but improvement is still needed for accurate early diagnosis. We evaluated the feasibility of a novel diagnosis index for early diagnosis of AD based on quantitative susceptibility mapping (QSM) and VBM. Thirty-seven patients with AD, 24 patients with mild cognitive impairment (MCI) due to AD, and 36 cognitively normal (NC) subjects from four centers were included. A hybrid sequence was performed by using 3-T MRI with a 3D multi-echo GRE sequence to obtain both a T1-weighted image for VBM and phase images for QSM. The index was calculated from specific voxels in QSM and VBM images by using a linear support vector machine. The method of voxel extraction was optimized to maximize diagnostic accuracy, and the optimized index was compared with the conventional VBM-based index using receiver operating characteristic analysis. The index was optimal when voxels were extracted as increased susceptibility (AD > NC) in the parietal lobe and decreased gray matter volume (AD < NC) in the limbic system. The optimized proposed index showed excellent performance for discrimination between AD and NC (AUC = 0.94, p = 1.1 × 10-10) and good performance for MCI and NC (AUC = 0.87, p = 1.8 × 10-6), but poor performance for AD and MCI (AUC = 0.68, p = 0.018). Compared with the conventional index, AUCs were improved for all cases, especially for MCI and NC (p < 0.05). In this preliminary study, the proposed index based on QSM and VBM improved the diagnostic performance between MCI and NC groups compared with the VBM-based index. • We developed a novel diagnostic index for Alzheimer's disease based on quantitative susceptibility mapping (QSM) and voxel-based morphometry (VBM). • QSM and VBM images can be acquired simultaneously in a single sequence with little increasing scan time. • In this preliminary study, the proposed diagnostic index improved the discriminative performance between mild cognitive impairment and normal control groups compared with the conventional VBM-based index.

This study aimed to investigate the association between iron content in grey matter (GM) nuclei and functional outcome in acute ischaemic stroke (AIS) patients utilizing quantitative susceptibility mapping. Forty AIS patients and 40 age-, sex- and education-matched healthy controls underwent quantitative susceptibility mapping to assess susceptibility values, which are positively correlated with iron content, in the caudate nucleus, putamen, globus pallidus, thalamus, red nucleus and substantia nigra. The nuclei on the contralateral side were measured in AIS patients to minimize confounding due to oedema or haemorrhage. Functional outcome was determined by the modified Rankin Scale (mRS) score at 3 months after stroke. Poor outcome was defined as mRS >2, whilst a good outcome was defined as ≤2. Susceptibility values were significantly higher in most contralateral GM nuclei in AIS patients than in the corresponding left or right nuclei in healthy controls. AIS patients with poor outcome showed significantly lower susceptibility value than those with good outcome in the contralateral caudate nucleus, but no significant differences were observed in other GM nuclei. Binary logistic regression analysis revealed a significant association between the susceptibility value of the contralateral caudate nucleus and poor outcome after adjustment for confounders (adjusted odds ratio 0.692, 95% confidence interval 0.486-0.986, p = 0.042). Receiver operating characteristic curve analysis showed an acceptable ability of the susceptibility value of the contralateral caudate nucleus to predict poor outcome (area under the curve 0.740, p = 0.013). Lower iron content in the contralateral caudate nucleus was associated with poor functional outcome in AIS patients.

Iron quantification in Parkinson's disease using an age-based threshold on susceptibility maps: The advantage of local versus entire structure iron content measurements

ObjectiveIn dynamic susceptibility contrast MRI (DSC-MRI), an arterial input function (AIF) is required to quantify perfusion. However, estimation of the concentration of contrast agent (CA) from magnitude MRI signal data is challenging. A reasonable alternative would be to quantify CA concentration using quantitative susceptibility mapping (QSM), as the CA alters the magnetic susceptibility in proportion to its concentration.Material and methodsAIFs with reasonable appearance, selected on the basis of conventional criteria related to timing, shape, and peak concentration, were registered from both ΔR2* and QSM images and mutually compared by visual inspection. Both ΔR2*- and QSM-based AIFs were used for perfusion calculations based on tissue concentration data from ΔR2*as well as QSM images.ResultsAIFs based on ΔR2* and QSM data showed very similar shapes and the estimated cerebral blood flow values and mean transit times were similar. Analysis of corresponding ΔR2* versus QSM-based concentration estimates yielded a transverse relaxivity estimate of 89 s−1 mM−1, for voxels identified as useful AIF candidate in ΔR2* images according to the conventional criteria.DiscussionInterestingly, arterial concentration time curves based on ΔR2* versus QSM data, for a standard DSC-MRI experiment, were generally very similar in shape, and the relaxivity obtained in voxels representing blood was similar to tissue relaxivity obtained in previous studies.

Purpose: This study aimed to detect changes in iron deposition and neural microstructure in the substantia nigra (SN), red nucleus (RN), and basal ganglia of Parkinson's disease (PD) patients at different stages using quantitative susceptibility mapping and diffusion kurtosis imaging to identify potential indicators of early-stage PD. Methods: We enrolled 20 early-stage and 15 late-stage PD patients, as well as 20 age- and sex-matched controls. All participants underwent quantitative susceptibility mapping and diffusion kurtosis imaging to determine magnetic susceptibility (MS), fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) in several brain regions. Results: Compared with the control group, MS and MK values in the SN were significantly increased in the early- and late-stage PD group, whereas MS values in the red nucleus (RN), globus pallidus (GP), and caudate nucleus (CN), FA value in the CN and GP, and MK value in the CN and putamen (PU) were significantly increased in the late-stage PD group. There were positive correlations between MS and MK values in the CN and MS and FA values in the GP. Furthermore, the combination of MS and MK values in the SN provided high accuracy for distinguishing early-stage PD patients from controls. Conclusions: This study identified MS and MK in the SN as potential indicators of early-stage PD.

As previous studies reported, gadolinium deposits in globus pallidus (GP) and dentate nucleus (DN) after repeated administrations of gadolinium-based contrast agents (GBCAs) and a signal intensity (SI) increase on T1-weighted images were related to linear GBCAs, not macrocyclic GBCAs. To identify whether quantitative susceptibility mapping (QSM) could measure a subtle increase in magnetic susceptibility in DN and GP in patients after repeated administrations of gadoteric acid meglumine (Gd-DOTA). In this study, 50 patients with cerebral tumors who had received at least three injections of Gd-DOTA (GBCA group) and 50 individuals without a history of GBCA injections (non-GBCA group) were included. The image data for QSM and T1-weighted images were reviewed. Spearman rank correlation was used to estimate the associations between the values (magnetic susceptibility of QSM and SI ratios of T1-weighted images) and the number of Gd-DOTA injections. The mean magnetic susceptibility of GP in GBCA group was 0.136 ± 0.031 ppm, which was significantly higher than that in control group (0.114 ± 0.030 ppm) (P = 0.001). In the GBCA group (n = 50), we found a substantial positive correlation between magnetic susceptibility of GP and the number of Gd-DOTA injections according to Spearman rank correlation coefficient (ρ = 0.673, P = 0.0001). There was a modest but significant correlation between magnetic susceptibility of DN and the number of Gd-DOTA injections (ρ = 0.311, P = 0.028). In comparison to the control group, the magnetic susceptibility of GP in the GBCA group was significantly higher and had a substantial positive association with the number of Gd-DOTA injections.

Myotonic dystrophy type 1 is a dominantly inherited disorder, affecting musculoskeletal and central nervous systems and mainly characterized by progressive muscular atrophy and multisystemic damages including cardiac, respiratory and sleep dysfunctions. Neuroimaging studies conducted in myotonic dystrophy type 1 patients have documented widespread cerebral alterations encompassing structural, microstructural, functional and metabolic aspects of the brain, while comparatively few studies have investigated the role of iron concentration in the pathophysiology of central nervous system impairment. We report here the use of quantitative susceptibility (χ) mapping to explore iron content of both cortical and subcortical structures in myotonic dystrophy type 1 patients and to assess its possible clinical relevance, combining imaging and clinical data. Thirty-four myotonic dystrophy type 1 participants (20 females, 46.8 ± 12.0 years old) and 35 age- and sex- matched healthy controls (20 females, 50.5 ± 17.3 years old) were included in the study. All participants underwent MRI examinations in the same 3-Tesla scanner. The MRI protocol included 3D morphological T1-weighted magnetization prepared rapid gradient echo and T2*weighted multi-echo gradient echo for quantitative susceptibility mapping reconstruction. Cortical and subcortical structures were automatically segmented, and a volume of interest–based analysis was performed; χ distributions were compared between the two groups and myotonic dystrophy type 1 χ values were correlated with clinical and laboratory data. In the myotonic dystrophy type 1 group, a significant increase of χ was found in almost all cortical gyri, as a non-specific sign of neurodegeneration. Among subcortical structures, χ was significantly higher in myotonic dystrophy type 1 group in both thalamus (ventral and pulvinar nuclei) and brainstem (pons and medulla), compared to healthy controls. Additionally, correlation analysis showed some links between χ in subcortical structures and clinical signs, suggesting greater iron concentration with deterioration of clinical conditions. Thalamic χ values were associated with cardiological parameters and disability scores and, as with brainstem χ, they were also positively correlated with the number of central apnoeas; finally, thalamic and brainstem χ were negatively correlated with the age of onset. This study showed a correlation between autonomic dysfunction related to certain subcortical structures and their χ; higher values of χ correlated with greater functional impairment, suggesting iron accumulation detected by the quantitative susceptibility mapping technique is a possible biomarker of disease progression.

To explore the changes of brain susceptibility of different sides and genders in healthy young adults using quantitative susceptibility mapping (QSM). Totally 42 healthy young right-handed adults underwent conventional brain magnetic resonance imaging and QSM scans, and the susceptibility maps were obtained by image post-processing software. Then the regions-of-interest (ROI) of bilateral frontal gray matter (FGM), frontal white matter (FWM), caudate (CA), globus pallidus (GP), putamen (PU), thalamus (TH), substantia nigra (SN), red nucleus (RN), dentate nucleus (DN), pons (PO), and corpus callosum (CC) were manually drawn to obtain magnetic susceptibility on the susceptibility maps. The magnetic susceptibility of each ROI was compared between 2 sides and genders by Wilcoxon rank sum test. Magnetic susceptibility of bilateral ROI was the highest in GP, followed by SN, and the lowest in FWM. No statistically significant difference was found in susceptibility of bilateral FGM, FWM, CA, GP, PU, TH, SN, RN, DN, PO, or CC. Magnetic susceptibility in CA significantly different genders. Brain magnetic susceptibility measured by QSM can be used to quantitatively assess brain iron concentrations.

The aims of this study were to investigate and validate quantitative susceptibility mapping (QSM) for lesional iron quantification in cerebral cavernous malformations (CCMs). Magnetic resonance imaging studies were performed in phantoms and 16 patients on a 3-T scanner. Susceptibility weighted imaging, QSM, and R2* maps were reconstructed from in vivo data acquired with a 3-dimensional, multi-echo, and T2*-weighted gradient echo sequence. Magnetic susceptibility measurements were correlated to susceptibility weighted imaging and R2* results. In addition, iron concentrations from surgically excised CCM lesion specimens were determined using inductively coupled plasma mass spectrometry and correlated with QSM measurements. The QSM images demonstrated excellent image quality for depicting CCM lesions in both sporadic and familial cases. Susceptibility measurements revealed a positive linear correlation with R2* values (R(2) = 0.99 for total, R(2) = 0.69 for mean; P < 0.01). Quantitative susceptibility mapping values of known iron-rich brain regions matched closely with those of previous studies and in interobserver consistency. A strong correlation was found between QSM and the concentration of iron phantoms (0.925; P < 0.01), as well as between QSM and mass spectroscopy estimation of iron deposition (0.999 for total iron, 0.86 for iron concentration; P < 0.01) in 18 fragments of 4 excised human CCM lesion specimens. The ability of QSM to evaluate iron deposition in CCM lesions was illustrated via phantom, in vivo, and ex vivo validation studies. Quantitative susceptibility mapping may be a potential biomarker for monitoring CCM disease activity and response to treatments.