Multimodal Investigation of Deep Gray Matter Nucleus in Patients with Multiple Sclerosis and Their Clinical Correlations: A Multivariate Pattern Analysis Study.

Deep gray matter (DGM) nucleus are involved in patients with multiple sclerosis (MS) and are strongly associated with clinical symptoms. We used machine learning approach to further explore microstructural alterations in DGM of MS patients. One hundred and fifteen MS patients and seventy-one healthy controls (HC) underwent brain MRI. The fractional anisotropy (FA), mean diffusivity (MD), quantitative susceptibility value (QSV) and volumes of the caudate nucleus (CN), putamen (PT), globus pallidus (GP), and thalamus (TH) were measured. Multivariate pattern analysis, based on a machine-learning algorithm, was applied to investigate the most damaged regions. Partial correlation analysis was used to investigate the correlation between MRI quantitative metrics and clinical neurological scores. The area under the curve of FA-based classification model was 0.83, while they were 0.93 for MD and 0.81 for QSV. The Montreal cognitive assessment scores were correlated with the volume of the DGM and the expanded disability status scale scores were correlated with the MD of the GP and PT. The study results indicated that MS patients had involvement of DGM with the CN being the most affected. The atrophy of DGM in MS patients mainly affected cognitive function and the microstructural damage of DGM was mainly correlated with clinical disability.

Dual-energy CT of the pancreas: comparison between virtual non-contrast images and true non-contrast images in the detection of pancreatic lesion.

PURPOSE: To evaluate the image quality and diagnostic performance for pancreatic lesion between true non-contrast (TNC) and virtual non-contrast (VNC) images obtained from the dual-energy computed tomography (DECT). METHODS: One hundred six patients with pancreatic mass underwent contrast-enhanced DECT examinations were retrospectively included in this study. VNC images of the abdomen were generated from late arterial (aVNC) and portal (pVNC) phases. For quantitative analysis, the attenuation differences and reproducibility of abdominal organs were compared between TNC and aVNC/pVNC measurements. Qualitatively image quality was assessed by two radiologists using a five-point scale, and they independently compared the detection accuracy of pancreatic lesions between TNC and aVNC/pVNC images. The volume CT dose index (CTDIvol) and size-specific dose estimates (SSDE) were recorded to evaluate the potential dose reduction when using VNC reconstruction to replace the unenhanced phase. RESULTS: A total of 78.38% (765/976) of the attenuation measurement pairs were reproducible between TNC and aVNC images, and 71.0% (693/976) between TNC and pVNC images. In triphasic examinations, a total of 108 pancreatic lesions were found in 106 patients, and no significant difference in detection accuracy was found between TNC and VNC images (p = 0.587-0.957). Qualitatively, image quality was rated diagnostic (score ≥ 3) in all the VNC images. Calculated CTDIvol and SSDE reduction of about 34% could be achieved by omitting the non-contrast phase. CONCLUSION: VNC images of DECT provide diagnostic image quality and accurate pancreatic lesions detection, which are a promising alternative to unenhanced phase with a substantial reduction of radiation exposure in clinical routine.

Diffusion kurtosis imaging and diffusion tensor imaging parameters applied to white matter and gray matter of patients with anti-N-methyl-D-aspartate receptor encephalitis.

Objectives: To compare parameters of diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) to evaluate which can better describe the microstructural changes of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients and to characterize the non-Gaussian diffusion patterns of the whole brain and their correlation with neuropsychological impairments in these patients. Materials and methods: DTI and DKI parameters were measured in 57 patients with anti-NMDAR encephalitis and 42 healthy controls. Voxel-based analysis was used to evaluate group differences between white matter and gray matter separately. The modified Rankin Scale (mRS) was used to evaluate the severity of the neurofunctional recovery of patients, the Montreal Cognitive Assessment (MoCA) was used to assess global cognitive performance, and the Hamilton Depression Scale (HAMD) and fatigue severity scale (FSS) were used to evaluate depressive and fatigue states. Results: Patients with anti-NMDAR encephalitis showed significantly decreased radial kurtosis (RK) in the right extranucleus in white matter (P < 0.001) and notably decreased kurtosis fractional anisotropy (KFA) in the right precuneus, the right superior parietal gyrus (SPG), the left precuneus, left middle occipital gyrus, and left superior occipital gyrus in gray matter (P < 0.001). Gray matter regions with decreased KFA overlapped with those with decreased RK in the left middle temporal gyrus, superior temporal gyrus (STG), supramarginal gyrus (SMG), postcentral gyrus (POCG), inferior parietal but supramarginal gyrus, angular gyrus (IPL) and angular gyrus (ANG) (P < 0.001). The KFA and RK in the left ANG, IPL and POCG correlated positively with MoCA scores. KFA and RK in the left ANG, IPL, POCG and SMG correlated negatively with mRS scores. KFA in the left precuneus and right SPG as well as RK in the left STG correlated negatively with mRS scores. No significant correlation between KFA and RK in the abnormal brain regions and HAMD and FSS scores was found. Conclusion: The microstructural changes in gray matter were much more extensive than those in white matter in patients with anti-NMDAR encephalitis. The brain damage reflected by DKI parameters, which have higher sensitivity than parameters of DTI, correlated with cognitive impairment and the severity of the neurofunctional recovery.

Dual-energy CT with virtual monoenergetic images and iodine maps improves tumor conspicuity in patients with pancreatic ductal adenocarcinoma.

OBJECTIVES: To evaluate the value of monoenergetic images (MEI [+]) and iodine maps in dual-source dual-energy computed tomography (DECT) for assessing pancreatic ductal adenocarcinoma (PDAC), including the visually isoattenuating PDAC. MATERIALS AND METHODS: This retrospective study included 75 PDAC patients, who underwent contrast-enhanced DECT examinations. Conventional polyenergetic image (PEI) and 40-80 keV MEI (+) (10-keV increments) were reconstructed. The tumor contrast, contrast-to-noise ratio (CNR) of the tumor and peripancreatic vessels, the signal-to-noise ratio (SNR) of the pancreas and tumor, and the tumor diameters were quantified. On iodine maps, the normalized iodine concentration (NIC) in the tumor and parenchyma was compared. For subjective analysis, two radiologists independently evaluated images on a 5-point scale. RESULTS: All the quantitative parameters were maximized at 40-keV MEI (+) and decreased gradually with increasing energy. The tumor contrast, SNR of pancreas and CNRs in 40-60 keV MEI (+) were significantly higher than those in PEI (p < 0.05). For visually isoattenuating PDAC, 40-50 keV MEI (+) provided significantly higher tumor CNR compared to PEI (p < 0.05). The reproducibility in tumor measurements was highest in 40-keV MEI (+) between the two radiologists. The tumor and parenchyma NIC were 1.28 ± 0.65 and 3.38 ± 0.72 mg/mL, respectively (p < 0.001). 40-50 keV MEI (+) provided the highest subjective scores, compared to PEI (p < 0.001). CONCLUSIONS: Low-keV MEI (+) of DECT substantially improves the subjective and objective image quality and consistency of tumor measurements in patients with PDAC. Combining the low-keV MEI (+) and iodine maps may yield diagnostically adequate tumor conspicuity in visually isoattenuating PDAC.

Clinical Variables, Deep Learning and Radiomics Features Help Predict the Prognosis of Adult Anti-N-methyl-D-aspartate Receptor Encephalitis Early: A Two-Center Study in Southwest China.

Objective: To develop a fusion model combining clinical variables, deep learning (DL), and radiomics features to predict the functional outcomes early in patients with adult anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in Southwest China. Methods: From January 2012, a two-center study of anti-NMDAR encephalitis was initiated to collect clinical and MRI data from acute patients in Southwest China. Two experienced neurologists independently assessed the patients' prognosis at 24 moths based on the modified Rankin Scale (mRS) (good outcome defined as mRS 0-2; bad outcome defined as mRS 3-6). Risk factors influencing the prognosis of patients with acute anti-NMDAR encephalitis were investigated using clinical data. Five DL and radiomics models trained with four single or combined four MRI sequences (T1-weighted imaging, T2-weighted imaging, fluid-attenuated inversion recovery imaging and diffusion weighted imaging) and a clinical model were developed to predict the prognosis of anti-NMDAR encephalitis. A fusion model combing a clinical model and two machine learning-based models was built. The performances of the fusion model, clinical model, DL-based models and radiomics-based models were compared using the area under the receiver operating characteristic curve (AUC) and accuracy and then assessed by paired t-tests (P < 0.05 was considered significant). Results: The fusion model achieved the significantly greatest predictive performance in the internal test dataset with an AUC of 0.963 [95% CI: (0.874-0.999)], and also significantly exhibited an equally good performance in the external validation dataset, with an AUC of 0.927 [95% CI: (0.688-0.975)]. The radiomics_combined model (AUC: 0.889; accuracy: 0.857) provided significantly superior predictive performance than the DL_combined (AUC: 0.845; accuracy: 0.857) and clinical models (AUC: 0.840; accuracy: 0.905), whereas the clinical model showed significantly higher accuracy. Compared with all single-sequence models, the DL_combined model and the radiomics_combined model had significantly greater AUCs and accuracies. Conclusions: The fusion model combining clinical variables and machine learning-based models may have early predictive value for poor outcomes associated with anti-NMDAR encephalitis.

Reproducibility and feasibility of optic nerve diffusion MRI techniques: single-shot echo-planar imaging (EPI), readout-segmented EPI, and reduced field-of-view diffusion-weighted imaging.

BACKGROUND: Diffusion-weighted imaging (DWI) is an essential technique for optic nerve diseases. However, the image quality of optic nerve DWI is decreased by the distortions and artifacts associated with conventional techniques. In order to establish this method as a critical tool in optic nerve diseases, reproducibility and feasibility of new technical and conventional approaches of DWI need to be systematically investigated. METHODS: DWIs were acquired using ss-EPI, readout-segmented EPI (rs-EPI) DWI, and reduced field-of-view (rFOV) DWI. 26 volunteers (mean age 31.2 years) underwent repeated MRI examinations in order to assess scan-rescan reproducibility and accuracy. The apparent diffusion coefficient (ADC) values (three ROIs were measured on each side) were determined to evaluate the reproducibility of each sequence and the differences between the three techniques. To quantify the geometric distortion artifacts, the length of optic nerve and the maximum angle of optic nerve were defined and compared to T2-weighted imaging. In addition, two readers evaluated four different aspects of image quality on 5-point Likert scales. RESULTS: rs-EPI DWI (ICCs: 0.916, 0.797 and 0.781) and rFOV DWI (ICCs: 0.850, 0.595 and 0.750) showed higher reproducibility (ICCs: ROI1, ROI2 and ROI3) of mean ADC value in all three ROIs than ss-EPI DWI (ICCs: 0.810, 0.442 and 0.379). The quantitative analysis of geometric distortion yielded a higher agreement of both rs-EPI DWI and rFOV DWI with T2-weighted imaging than ss-EPI. rs-EPI DWI (2.38 ± 0.90) and rFOV DWI (2.46 ± 0.58) were superior to ss-EPI DWI (1.58 ± 0.64) with respect to overall image quality and other aspects of image quality, each with P < 0.05. The mean ADC values of rFOV DWI were significantly lower than those of rs-EPI DWI and ss-EPI DWI in all three ROIs (P < 0.001). CONCLUSIONS: Both rs-EPI DWI and rFOV-EPI DWI are suitable techniques for the assessment of diffusion restriction and provide significantly improved image quality compared with ss-EPI DWI. For methods using the same acquisition time, rFOV DWI is superior to ss-EPI DWI, while rs-EPI showed an overall superiority, although this technique took 47% longer to perform.

ANGPTL4 negatively regulates the progression of osteosarcoma by remodeling branched-chain amino acid metabolism.

Angiopoietin-like-4 (ANGPTL4), a secreted glycoprotein that is mainly known as a regulator in lipid metabolism, now, is also indicated to be involved in the regulation of cancer progression and metastasis. However, little is known about not only biological functions, but also underlying mechanism of ANGPTL4 in the progression of osteosarcoma (OS). Here, we discovered that ANGPTL4 is downregulated in OS, and is associated with branched-chain amino acid (BCAA) metabolism. The BCAAs (valine, leucine, and isoleucine) are essential amino acids that play an important role in metabolic regulation. Aberrant BCAA metabolism is also found in various cancers and is associated with tumor progression, including proliferation, invasion, and metastasis. In this study, we indicated that the negative relation between the expression of ANGPTL4 and BCAA catabolism in OS samples and cell lines. The knockdown of ANGPTL4 in OS cells resulted in the accumulation of BCAAs, which in turn activated the mTOR signaling pathway, enhancing OS cell proliferation. Thus, reduced expression of ANGPTL4 is associated with the progression of OS. Taken together, our results demonstrated that the ANGPTL4/BCAA/mTOR axis is an important pathway in OS progression and may be a potential therapeutic target to slow OS progression.

Dual-energy CT with virtual monoenergetic images to improve the visualization of pancreatic supplying arteries: the normal anatomy and variations.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a malignancy with poor prognosis, appropriate surgical resection and neoadjuvant therapy depend on the accurate identification of pancreatic supplying arteries. We aim to evaluate the ability of monoenergetic images (MEI [+]) of dual-energy CT (DECT) to improve the visualization of pancreatic supplying arteries compared to conventional polyenergetic images (PEI) and investigate the implications of vascular variation in pancreatic surgery and transarterial interventions. RESULTS: One hundred patients without pancreatic diseases underwent DECT examinations were retrospectively enrolled in this study. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) at 40-keV MEI (+) were significantly higher than those of PEI (p < 0.05). All subjective MEI (+) scores were significantly higher than those of PEI (p < 0.05). The visualization rates were significantly higher for posterior superior pancreaticoduodenal artery (PSPDA), anterior and posterior inferior pancreaticoduodenal artery (AIPDA, PIPDA), anterior and posterior pancreaticoduodenal arcade (APAC, PPAC), transverse and caudal pancreatic artery (TPA, PCA) at 40-keV MEI (+) than those of PEI (p < 0.05). However, there were no significant differences for visualizing anterior superior pancreaticoduodenal artery (ASPDA), inferior pancreaticoduodenal artery (IPDA), dorsal and magnificent pancreatic artery (DPA, MPA) between 40-keV MEI (+) and PEI (p > 0.05). Four types of variations were observed in the origin of DPA and three to five types in the origin of PSPDA, AIPDA and PIPDA. CONCLUSIONS: 40-keV MEI (+) of DECT improves the visualization and objective and subjective image quality of pancreatic supplying arteries compared to PEI. Pancreatic supplying arteries have great variations, which has important implications for preoperative planning of technically challenging surgeries and transarterial interventions.

pH-Responsive Oxygen and Hydrogen Peroxide Self-Supplying Nanosystem for Photodynamic and Chemodynamic Therapy of Wound Infection.

The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) has been continuously explored in the antibacterial aspect and has achieved more effective antibacterial effect than a single therapy. We design a pH-responsive O2 and H2O2 self-supplying zeolitic imidazolate framework-67 (ZIF-67) nanosystem for PDT/CDT of wound infection. Under the acidic inflammatory conditions, ZIF-67 can degrade to produce Co2+ and release CaO2 and graphene quantum dots (GQDs). The exposed CaO2 reacted with water to generate H2O2 and O2. The self-supplied O2 alleviates hypoxia at the site of inflammation and enhances external light-initiated GQD-mediated PDT, while H2O2 was catalyzed by endogenous Co2+ to produce hydroxyl radicals for Co2+-triggered CDT. In vitro and in vivo experiments confirm that CaO2/GQDs@ZIF-67 has a combined PDT/CDT effect. The antibacterial mechanism indicates that bacteria post-treated with CaO2/GQDs@ZIF-67 may be sterilized by reactive oxygen species-mediated oxidative stress and the leakage of bacterial contents. The experiments also find that CaO2/GQDs@ZIF-67 may activate the immune response and enhance the therapeutic effect by activating the cyclic GMP-AMP synthase-stimulator of interferon genes signaling pathway.

The ultrafast, high-pitch turbo FLASH mode of third-generation dual-source CT: Effect of different pitch and corresponding SFOV on image quality in a phantom study.

PURPOSE: To investigate the effect of different pitches and corresponding scan fields of view (SFOVs) on the image quality in the ultrafast, high-pitch turbo FLASH mode of the third-generation dual-source CT using an anthropomorphic phantom. METHODS: The phantom was scanned using the ultrafast, high-pitch turbo FLASH protocols of the third-generation dual-source CT with the different pitches and corresponding SFOVs (pitches: 1.55 to 3.2 with increments of 0.1, SFOVs: 50 cm to 35.4 cm). The objective parameters such as the CT number, image noises, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and artifacts index (AI), and image features from the head, chest, and abdomen were compared between the CT images with a pitch of 1.55 and SFOV of Ø 50 cm and a pitch of 3.2 and SFOV of Ø 35.4 cm. Then, the 18 series of CT images of the head, chest, and abdomen were evaluated by three radiologists independently. RESULTS: The differences in the CT numbers were not statically significant between the CT images with a pitch of 1.55 and SFOV of Ø 50 cm and a pitch of 3.2 and SFOV of Ø 35.4 cm from most body parts and potential combinations (p > 0.05), Most of the image noises and the AI from the images with the pitch of 1.55 were significantly lower than those with the pitch of 3.2 (p < 0.05), and the SNR and CNR from the images with the pitch of 1.55 were higher than those with the pitch of 3.2. There were significant differences in the first-order features and texture features of the head (59.3%, 28.3%), chest (66%, 35.7%), and abdomen (71.6%, 64.7%) (p < 0.05). The subjective image quality was excellent when the pitch was less than 2.0 and gradually decreased with the increasing pitch. In addition, the image quality decreased significantly when the pitch was higher than 3.0 (all k≥0.69), especially in the head and chest. CONCLUSIONS: In the ultrafast, high-pitch turbo FLASH mode of the third-generation DSCT, increasing the pitch and lowering the corresponding SFOV will change the image features and cause more artifacts degrading the image quality. Specific to the clinical needs, decreasing the pitch not only can expand the SFOV but also can improve the image quality.

Demyelination and remyelination detected in an alternative cuprizone mouse model of multiple sclerosis with 7.0 T multiparameter magnetic resonance imaging.

The aim of this study was to investigate the mechanisms underlying demyelination and remyelination with 7.0 T multiparameter magnetic resonance imaging (MRI) in an alternative cuprizone (CPZ) mouse model of multiple sclerosis (MS). Sixty mice were divided into six groups (n = 10, each), and these groups were imaged with 7.0 T multiparameter MRI and treated with an alternative CPZ administration schedule. T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and diffusion tensor imaging (DTI) were used to compare the splenium of the corpus callosum (sCC) among the groups. Prussian blue and Luxol fast blue staining were performed to assess pathology. The correlations of the mean grayscale value (mGSV) of the pathology results and the MRI metrics were analyzed to evaluate the multiparameter MRI results. One-way ANOVA and post hoc comparison showed that the normalized T2WI (T2-nor), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were significantly different among the six groups, while the mean phase (Φ) value of SWI was not significantly different among the groups. Correlation analysis showed that the correlation between the T2-nor and mGSV was higher than that among the other values. The correlations among the FA, RD, MD, and mGSV remained instructive. In conclusion, ultrahigh-field multiparameter MRI can reflect the pathological changes associated with and the underlying mechanisms of demyelination and remyelination in MS after the successful establishment of an acute CPZ-induced model.

Optic radiations are thinner and show signs of iron deposition in patients with long-standing remitting-relapsing multiple sclerosis: an enhanced T2*-weighted angiography imaging study.

OBJECTIVE: This study aimed to investigate iron deposition and thickness and signal changes in optic radiation (OR) by enhanced T2*-weighted angiography imaging (ESWAN) in patients with relapsing-remitting multiple sclerosis (RRMS) with unilateral and bilateral lesions or no lesions. METHODS: Fifty-one RRMS patients (42 patients with a disease duration [DD] ≥ 2 years [group Mor], nine patients with a DD < 2 years [group Les]) and 51 healthy controls (group Con) underwent conventional magnetic resonance imaging (MRI) and ESWAN at 3.0 T. The mean phase value (MPV) of the OR was measured on the phase image, and thickness and signal changes of the OR were observed on the magnitude image. RESULTS: The average MPVs for the OR were 1,981.55 ± 7.75 in group Mor, 1,998.45 ± 2.01 in group Les, and 2,000.48 ± 5.53 in group Con. In group Mor, 28 patients with bilateral OR lesions showed bilateral OR thinning with a heterogeneous signal, and 14 patients with unilateral OR lesions showed ipsilateral OR thinning with a heterogeneous signal. In the remaining nine patients without OR lesions and in group Con, the bilateral OR had a normal appearance. In the patients, a negative correlation was found between DD and OR thickness and a positive correlation was found between MPV and OR thickness. CONCLUSIONS: We confirmed iron deposition in the OR in the RRMS patients, and the OR thickness was lower in the patients than in the controls. KEY POINTS: • Enhanced T 2* -weighted magnetic resonance angiography (ESWAN) provides new insights into multiple sclerosis (MS). • Focal destruction of the optic radiation (OR) is detectable by ESWAN. • Iron deposition in OR can be measured on ESWAN phase image in MS patients. • OR thickness was lower in the patients than in the controls. • Iron deposition and thickness changes of the OR are associated with disease duration.

Dynamic contrast-enhanced magnetic resonance imaging for differentiating osteomyelitis from acute neuropathic arthropathy in the complicated diabetic foot.

OBJECTIVE: The main purpose of this study was to investigate the diagnostic value of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating osteomyelitis from acute neuropathic arthropathy in the diabetic foot. MATERIALS AND METHODS: This prospective study was carried out on 30 diabetic foot patients, with a mean age of 51 years. The patients all underwent clinical examinations, laboratory examinations and DCE-MRI. The DCE-MRI parameters (Ktrans, Kep and Ve) of the regions of acute neuropathic arthropathy and osteomyelitis were calculated. Receiver operating characteristic curves (ROCs) were used to identify the DCE-MRI parameters that showed the highest accuracy in differentiating the acute neuropathic arthropathy from the osteomyelitic regions. Pearson correlation coefficients were used to assess the correlations among the DCE-MRI parameters, the level of C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR). RESULTS: The Ktrans, Kep and Ve values of the osteomyelitic regions were higher than those of the acute neuropathic arthropathy regions, and significant differences were found between the two groups (P = 0.000, P = 0.000, P = 0.000). The ROC analysis showed that Ktrans and Ve performed best in differentiating osteomyelitis from acute neuropathic arthropathy, both with an area under the curve of 0.938. The Pearson correlation coefficients showed that the DCE-MRI parameters correlated significantly with the level of CRP and ESR (P = 0.000, P = 0.014, P = 0.000; P = 0.000, P = 0.000, P = 0.013). CONCLUSIONS: Our results showed that DCE-MRI may provide reproducible parameters that can reliably differentiate osteomyelitis from acute neuropathic arthropathy.

Facial nerve schwannomas: A case series with an analysis of imaging findings.

Facial nerve schwannomas (FNSs) are rare benign tumors arising from the Schwann cells of the sheath of the facial nerve. These tumors may arise anywhere along the course of the facial nerve. Owing to their rarity and nonspecific clinical and radiological presentations, the preoperative diagnosis of FNSs is exceedingly difficult. In this study, we present four cases of histopathologically proven extratemporal schwannomas and a solitary case of intratemporal schwannoma. The purpose of this study was mainly focused on analyzing the imaging findings of extratemporal and intratemporal schwannomas in an effort to better characterize these lesions preoperatively. An early diagnosis of FNSs is helpful for the management and rehabilitation of these cases.

Iron deposition in the gray matter in patients with relapse-remitting multiple sclerosis: A longitudinal study using three-dimensional (3D)-enhanced T2*-weighted angiography (ESWAN).

PURPOSE: To investigate the relationship between the iron content by magnetic resonance imaging (MRI) and clinic correlation in patients with relapse-remitting multiple sclerosis (RRMS) over a two-year period. METHODS: Thirty RRMS patients and 30 healthy control subjects were examined twice, two years apart, by undergoing brain conventional MRI and three-dimensional (3D)-enhanced T2*-weighted angiography (ESWAN) sequences at 3.0T. Quantitative differences in iron content in deep gray matter (GM) nuclei and precentral gyrus GM between patients and control subjects with repeated-measures the mean phase values (MPVs) for ESWAN-filtered phase images. Spearman's rank correlation coefficient analysis was used to evaluate correlations of the MPVs, both 2-year-difference and single-time measurements, to disease duration, expanded disability status scale (EDSS) and times of recurrence. RESULTS: The RRMS patients had higher GM iron concentration than that of the healthy control subjects in both single-time measurements, but only the substantia nigra (SN), and the precentral gyrus GM (PGM) showed a significant statistical difference (p<0.05). Using the paired samples t test, we found that there were significant differences in two-year-difference measurements of the MPVs in the putamen (PUT), the globus pallidus (GP), the head of the caudate nucleus (HCN), the thalamus (THA), SN, the red nucleus (RN), the dentate nucleus (DN) and PGM, especially in SN (t=2.92, p=0.007) in RRMS patients. The MPVs of the PUT, GP, HCN, THA, SN, RN, DN and PGM for the subgroup with RRMS patients in times of recurrence less than twice were similar to the healthy controls. There was no significant difference in all regions of interests (ROIs). However, there were significant differences in all ROIs except THA and GP for the other subgroup with RRMS patients in times of recurrence more than and equal to twice. Spearman's rank correlation coefficient analysis showed there were significant negative correlations between disease duration and the MPVs in the HCN (r=-0.516, p=0.004), DN (r=-0.468, p=0.009) and PGM (r=-0.84, p=0). However, no correlations were found between the EDSS scores and the MPVs. CONCLUSIONS: Iron content in the GM can be measurable using MRI and our results confirmed that iron concentration was increasing in the GM of MS patients during two-year period compared to healthy controls. Furthermore, this study had also shown significant and substantial correlation of iron concentration with disease severity.