The changes of oxygen extraction fraction in different types of lesions in relapsing-remitting multiple sclerosis: A cross-sectional and longitudinal study.

OBJECTIVES: To explore the oxygen metabolism level of different types of lesions in relapsing-remitting multiple sclerosis (RRMS) patients by oxygen extraction fraction (OEF) both cross-sectionally and longitudinally. METHODS: Forty-six RRMS patients and forty-one healthy controls (HC) went MRI examination. The quantitative susceptibility mapping (QSM) and OEF map were reconstructed from a 3D multi-echo gradient echo sequence. MS lesions in white matter were classified as contrast-enhancing lesions (CELs) on post-gadolinium T1-weighted sequence, paramagnetic rim lesions (PRLs), hyperintense lesions and non-hyperintense lesions on QSM, respectively. The susceptibility and OEF of different types of lesions were compared. The susceptibility and OEF values were measured and compared among different types of lesions. Among these RRMS patients, seventeen had follow-up MRI and 232 lesions, and baseline to follow-up longitudinal changes in susceptibility and OEF were measured. RESULTS: PRLs had higher susceptibility and lower OEF than CELs, hyperintense lesions, and non-hyperintense lesions. The hyperintense lesions had higher susceptibility and lower OEF than non-hyperintense lesions. In longitudinal changes, PRLs had susceptibility increased (P < 0.001) and OEF decreased (P < 0.001). The hyperintense lesions showed significant decreases in susceptibility (P = 0.020), and non-hyperintense lesions showed significant increases in OEF during follow-up (P = 0.005). Notably, hyperintense lesions may convert to PRLs or non-hyperintense lesions as time progresses, accompanied by changes of OEF and susceptibility in the lesions. CONCLUSION: This study revealed tissue damage and oxygen metabolism level in different types of MS lesions. The OEF may contribute to further understanding the evolution of MS lesions.

Fractional anisotropy helps to differentiate the optic nerve impairment between neuromyelitis optica spectrum disorders and multiple sclerosis.

OBJECTIVES: To assess the characteristics of optic nerve impairment between neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) patients by fractional anisotropy (FA). METHODS: Thirty-one NMOSD patients, 25 MS patients, and 17 heathy controls (HC) who underwent optic nerve DTI were included. The optic nerves of the NMOSD and MS patients were divided into vision-impaired (VI) subgroups and normal-appearing (NA) subgroups according to visual status, respectively. FA values were measured in the anterior, middle, and posterior segments of each intraorbital optic nerve. RESULTS: FA values in VI NMOSD were significantly decreased in the whole optic nerve, especially the posterior segment of the optic nerve (p < 0.001). FA values measured in the anterior and middle segments of the optic nerve in VI MS were significantly decreased as compared to those in the HC (p < 0.05). Between NMOSD and MS, FA values in the posterior segment of the optic nerve showed significant differences (VI NMOSD vs. VI MS, 0.458 ± 0.097 vs. 0.568 ± 0.098, p < 0.001; NA NMOSD vs. NA MS, 0.568 ± 0.098 vs. 0.600 ± 0.085, p = 0.041, respectively). The signal intensity ratio (SIR) in the posterior segment of the optic nerve was significantly increased in VI NMOSD as compared with VI MS (p = 0.002). The combination of SIR and FA for distinguishing VI NMOSD from VI MS resulted in sensitivity, specificity, and positive and negative predictive values of 86.49%, 80.00%, 88.9%, and 76.2%, respectively. CONCLUSION: FA could quantify the characteristics of NMOSD- and MS-related optic nerve impairment. DTI was a simple and effective imaging tool to differentiate between the two. KEY POINTS: • NMOSD-related optic nerve impairment is extensive, often greater than half of the optic nerve, with the most significant involvement of the posterior segment of the optic nerve. • MS-related optic nerve impairment is more limited than NMOSD, and anterior and middle optic nerve involvement is common. • Optic nerve DTI is a convenient and effective imaging tool that can help characterize NMOSD and MS.

Automated adaptive preconditioner for quantitative susceptibility mapping.

PURPOSE: To develop an automated adaptive preconditioner for QSM reconstruction with improved susceptibility quantification accuracy and increased image quality. THEORY AND METHODS: The total field was used to rapidly produce an approximate susceptibility map, which was then averaged and trended over R2∗ binning to generate a spatially varying distribution of preconditioning values. This automated adaptive preconditioner was used to reconstruct QSM via total field inversion and was compared with its empirical counterparts in a numerical simulation, a brain experiment with 5 healthy subjects and 5 patients with intracerebral hemorrhage, and a cardiac experiment with 3 healthy subjects. RESULTS: Among evaluated preconditioners, the automated adaptive preconditioner achieved the fastest convergence in reducing the RMSE of the QSM in the simulation, suppressed hemorrhage-associated artifacts while preserving surrounding brain tissue contrasts, and provided cardiac chamber oxygenation values consistent with those reported in the literature. CONCLUSION: An automated adaptive preconditioner allows high-quality QSM from the total field in imaging various anatomies with dynamic susceptibility ranges.

Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions.

Chronic active multiple sclerosis lesions, characterized by a hyperintense rim of iron-enriched, activated microglia and macrophages, have been linked to greater tissue damage. Post-mortem studies have determined that chronic active lesions are primarily related to the later stages of multiple sclerosis; however, the occurrence of these lesions, and their relationship to earlier disease stages may be greatly underestimated. Detection of chronic active lesions across the patient spectrum of multiple sclerosis requires a validated imaging tool to accurately identify lesions with persistent inflammation. Quantitative susceptibility mapping provides efficient in vivo quantification of susceptibility changes related to iron deposition and the potential to identify lesions harbouring iron-laden inflammatory cells. The PET tracer 11C-PK11195 targets the translocator protein expressed by activated microglia and infiltrating macrophages. Accordingly, this study aimed to validate that lesions with a hyperintense rim on quantitative susceptibility mapping from both relapsing and progressive patients demonstrate a higher level of innate immune activation as measured on 11C-PK11195 PET. Thirty patients were enrolled in this study, 24 patients had relapsing remitting multiple sclerosis, six had progressive multiple sclerosis, and all patients had concomitant MRI with a gradient echo sequence and PET with 11C-PK11195. A total of 406 chronic lesions were detected, and 43 chronic lesions with a hyperintense rim on quantitative susceptibility mapping were identified as rim+ lesions. Susceptibility (relative to CSF) was higher in rim+ (2.42 ± 17.45 ppb) compared to rim- lesions (-14.6 ± 19.3 ppb, P < 0.0001). Among rim+ lesions, susceptibility within the rim (20.04 ± 14.28 ppb) was significantly higher compared to the core (-5.49 ± 14.44 ppb, P < 0.0001), consistent with the presence of iron. In a mixed-effects model, 11C-PK11195 uptake, representing activated microglia/macrophages, was higher in rim+ lesions compared to rim- lesions (P = 0.015). Validating our in vivo imaging results, multiple sclerosis brain slabs were imaged with quantitative susceptibility mapping and processed for immunohistochemistry. These results showed a positive translocator protein signal throughout the expansive hyperintense border of rim+ lesions, which co-localized with iron containing CD68+ microglia and macrophages. In conclusion, this study provides evidence that suggests that a hyperintense rim on quantitative susceptibility measure within a chronic lesion is a correlate for persistent inflammatory activity and that these lesions can be identified in the relapsing patients. Utilizing quantitative susceptibility measure to differentiate chronic multiple sclerosis lesion subtypes, especially chronic active lesions, would provide a method to assess the impact of these lesions on disease progression.

Amid proton transfer (APT) and magnetization transfer (MT) MRI contrasts provide complimentary assessment of brain tumors similarly to proton magnetic resonance spectroscopy imaging (MRSI).

OBJECTIVES: Using MRSI as comparison, we aimed to explore the difference between amide proton transfer (APT) MRI and conventional semi-solid magnetization transfer ratio (MTR) MRI, and to investigate if molecular APT and structural MTR can provide complimentary information in assessing brain tumors. METHODS: Seventeen brain tumor patients and 17 age- and gender-matched volunteers were included and scanned with anatomical MRI, APT and MT-weighted MRI, and MRSI. Multi-voxel choline (Cho) and N-acetylaspartic acid (NAA) signals were quantified from MRSI and compared with MTR and MTRasym(3.5ppm) contrasts averaged from corresponding voxels. Correlations between contrasts were explored voxel-by-voxel by pooling values from all voxels into Pearson's correlation analysis. Differences in correlation coefficients were tested with the Z-test (set at p<0.05). RESULTS: APT and MT provide good contrast and quantitative parameters in tumor imaging, as do the metabolite (Cho and NAA) maps. MTRasym(3.5ppm) significantly correlated with MTR (R=-0.61, p<0.0001), Cho (R=0.568, p<0.0001) and NAA (R=-0.619, p<0.0001) in tumors, and MTR also significantly correlated with Cho (R=-0.346, p<0.0001) and NAA (R=0.624, p<0.0001). In healthy volunteers, MTRasym(3.5ppm) was non-significantly correlated with MTR (R=-0.049, p=0.239), Cho (R=0.030, p=0.478) and NAA (R=-0.083, p=0.046). Significant correlations were found among MTR with Cho (R=0.199, p<0.0001) and NAA (R=0.263, p<0.0001) in the group of healthy volunteers with lower correlation R values than those in tumor patients. CONCLUSIONS: APT and MT could provide independent and supplementary information for the comprehensive assessment of molecular and structural changes due to brain tumor cancerogenesis. KEY POINTS: • MTR asym(3.5ppm) positively correlated with Cho while negatively with NAA in tumors. • MTR positively correlated with NAA while negatively with Cho in tumors. • Combining APT/MT provides molecular and structural information similarly to MRSI.

MEDI+0: Morphology enabled dipole inversion with automatic uniform cerebrospinal fluid zero reference for quantitative susceptibility mapping.

PURPOSE: To develop a quantitative susceptibility mapping (QSM) method with a consistent zero reference using minimal variation in cerebrospinal fluid (CSF) susceptibility. THEORY AND METHODS: The ventricular CSF was automatically segmented on the R2* map. An L2 -regularization was used to enforce CSF susceptibility homogeneity within the segmented region, with the averaged CSF susceptibility as the zero reference. This regularization for CSF homogeneity was added to the model used in a prior QSM method (morphology enabled dipole inversion [MEDI]). Therefore, the proposed method was referred to as MEDI+0 and compared with MEDI in a numerical simulation, in multiple sclerosis (MS) lesions, and in a reproducibility study in healthy subjects. RESULTS: In both the numerical simulations and in vivo experiments, MEDI+0 not only decreased the susceptibility variation within the ventricular CSF, but also suppressed the artifact near the lateral ventricles. In the simulation, MEDI+0 also provided more accurate quantification compared to MEDI in the globus pallidus, substantia nigra, corpus callosum, and internal capsule. MEDI+0 measurements of MS lesion susceptibility were in good agreement with those obtained by MEDI. Finally, both MEDI+0 and MEDI showed good and similar intrasubject reproducibility. CONCLUSION: QSM with a minimal variation in ventricular CSF is viable to provide a consistent zero reference while improving image quality. Magn Reson Med 79:2795-2803, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care.

Quantitative susceptibility mapping (QSM) has enabled magnetic resonance imaging (MRI) of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM technology may be regarded to be sufficiently developed and validated to warrant wide dissemination for clinical applications of imaging isotropic susceptibility, which is dominated by metals in tissue, including iron and calcium. These biometals are highly regulated as vital participants in normal cellular biochemistry, and their dysregulations are manifested in a variety of pathologic processes. Therefore, QSM can be used to assess important tissue functions and disease. To facilitate QSM clinical translation, this review aims to organize pertinent information for implementing a robust automated QSM technique in routine MRI practice and to summarize available knowledge on diseases for which QSM can be used to improve patient care. In brief, QSM can be generated with postprocessing whenever gradient echo MRI is performed. QSM can be useful for diseases that involve neurodegeneration, inflammation, hemorrhage, abnormal oxygen consumption, substantial alterations in highly paramagnetic cellular iron, bone mineralization, or pathologic calcification; and for all disorders in which MRI diagnosis or surveillance requires contrast agent injection. Clinicians may consider integrating QSM into their routine imaging practices by including gradient echo sequences in all relevant MRI protocols. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:951-971.

Monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles for imaging of epidermal growth factor receptor-targeted cells and gliomas.

The objective of this study was to successfully synthesize epidermal growth factor receptor monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles (EGFRmAb-SPIONs) and explore their biocompatibility and potential applications as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection of brain glioma in vivo. After conjugation of EGFRmAb with SPIONs, the magnetic characteristics of EGFRmAb-SPIONs were investigated. Thereafter, the targeting abilities of EGFRmAb-SPIONs with MRI were qualitatively and quantitatively assessed in EGFR-positive C6 glioma cells in vitro and in a Wistar rat model bearing C6 glioma in vivo. Furthermore, the preliminary biocompatibility and toxicity of EGFRmAb-SPIONs were evaluated in normal rats through hematology assays and histopathologic analyses. Statistical analysis was performed using one-way analysis of variance and Student t-test, with a significance level of p < .05. From the results of EGFRmAb-SPION characterizations, the average particle size was 10.21 nm and the hydrodynamic diameter was 161.5 ± 2.12 nm. The saturation magnetization was 55 emu/g·Fe, and T2 relaxivity was 92.73 s-1mM-1 in distilled water. The preferential accumulation of the EGFRmAb-SPIONs within glioma and subsequent MRI contrast enhancement were demonstrated both in vitro in C6 cells and in vivo in rats bearing C6 glioma. After intravenous administration of EGFRmAb-SPIONs, T2-weighted MRI of the rat model with brain glioma exhibited an apparent hypointense region within glioma from 2 to 48 hours. The maximal image contrast was reached at 24 hours, where the signal intensity decreased and the R2 value increased by 30% compared to baseline. However, T2-weighted imaging of the rat model administered with SPIONs showed no visible signal changes within the tumor over the same time period. Moreover, no evident toxicities in vitro and in vivo with EGFRmAb-SPIONs were clearly identified based on the laboratory examinations. EGFRmAb-SPIONs could potentially be employed as a targeted contrast agent in the molecule-specific diagnosis of brain glioma in MRI.

Enlarged choroid plexus in relapsing-remitting multiple sclerosis may lead to brain structural changes through the glymphatic impairment.

OBJECTIVES: To investigate the potential link among choroid plexus (CP) volume, glymphatic clearance and brain structural change in relapsing-remitting multiple sclerosis (RRMS) patients. MATERIALS AND METHODS: Sixty-five RRMS patients and 48 healthy controls (HC) underwent MRI examination. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) was calculated to reflect glymphatic system function. The brain structure volume and DTI-ALPS index were compared between RRMS and HC. The mediating effect of the DTI-ALPS index between CP volume and brain structural changes was further investigated. The longitudinal changes of brain structure and DTI-ALPS index were compared in 20 RRMS patients. RESULTS: Compared to HC, CP volume in RRMS was significantly increased (P < 0.001), and DTI-ALPS index was significantly decreased (P = 0.001). The volumes of white matter, thalamus, putamen and pallidum were significantly decreased in RRMS, and the volumes of lateral ventricle and third ventricle were increased. Mediation analysis showed DTI-ALPS index partially mediated the association between CP enlargement and deep gray matter (DGM) atrophy in RRMS, and between CP enlargement and ventricle enlargement. CP volume and DTI-ALPS index were also significantly correlated with Expanded Disability Status Scale (EDSS) (P = 0.006, P = 0.043). Notably, the variation of DTI_ALPS index during the follow-up period were significantly and negatively correlated with the variation of EDSS (P = 0.045). CONCLUSION: Enlarged CP volume and decreased DTI_ALPS index may be closely related to DGM atrophy and ventricular enlargement in RRMS, and may be potential imaging markers of clinical disability.

SR-TTS: a rhyme-based end-to-end speech synthesis system.

Deep learning has significantly advanced text-to-speech (TTS) systems. These neural network-based systems have enhanced speech synthesis quality and are increasingly vital in applications like human-computer interaction. However, conventional TTS models still face challenges, as the synthesized speeches often lack naturalness and expressiveness. Additionally, the slow inference speed, reflecting low efficiency, contributes to the reduced voice quality. This paper introduces SynthRhythm-TTS (SR-TTS), an optimized Transformer-based structure designed to enhance synthesized speech. SR-TTS not only improves phonological quality and naturalness but also accelerates the speech generation process, thereby increasing inference efficiency. SR-TTS contains an encoder, a rhythm coordinator, and a decoder. In particular, a pre-duration predictor within the cadence coordinator and a self-attention-based feature predictor work together to enhance the naturalness and articulatory accuracy of speech. In addition, the introduction of causal convolution enhances the consistency of the time series. The cross-linguistic capability of SR-TTS is validated by training it on both English and Chinese corpora. Human evaluation shows that SR-TTS outperforms existing techniques in terms of speech quality and naturalness of expression. This technology is particularly suitable for applications that require high-quality natural speech, such as intelligent assistants, speech synthesized podcasts, and human-computer interaction.

The impact of paramagnetic rim lesions on cortical thickness and gray to white matter contrast in relapsing-remitting multiple sclerosis.

Background: Paramagnetic rim lesions (PRLs) on susceptibility magnetic resonance sequences have been suggested as an imaging marker of disease progression in multiple sclerosis. This retrospective cross-sectional study aimed to investigate the impact of PRLs on cortical thickness and gray matter (GM) to white matter (WM) contrast in relapsing-remitting multiple sclerosis (RRMS). Methods: A total of 82 RRMS patients (40 patients with at least 1 PRL and 42 patients without PRL) and 43 healthy controls (HC) were included in this study. The T1-weighted images (T1WI) were processed with the FreeSurfer pipeline. GM to WM signal intensity ratio (GWR) was obtained from T1WI by dividing the GM signal intensity by the WM signal intensity for each vertex. Group differences in cortical thickness and GWR were tested on reconstructed cortical surface. Results: Compared to HC, patients with PRL had thinner mean cortical thickness (P<0.001), higher mean GWR (P=0.001), and lower brain structure volumes (cortex volume, P=0.001; WM volume, P<0.001; deep GM volume, P<0.001). Vertex-based analysis found significant cortical thinning in several regions and increased GWR in a wider range of regions in patients with PRL. The two types of clusters had both overlapping regions and independent regions. However, in patients without PRL, only a few regions showed significant cortical thickness changes. Correlation analysis found that in patients with PRL, only PRL volume showed a significant negative correlation with mean cortical thickness (P=0.048), and PRL volume and count, non-PRL count, and total lesion volume were significantly and positively correlated with mean GWR (P<0.05). Conclusions: There were significant changes in cortical thickness, GWR, and brain structure volume in RRMS patients with PRL that may contribute to further understanding of the pathological mechanisms underlying neurological tissue damage.

Evaluating the diagnostic and therapeutic significance of KL-6 in patients with interstitial lung diseases.

Background: This study aimed to assess the diagnostic value of Krebs von den Lungen-6 (KL-6), Surfactant protein-A (SP-A), SP-D and molecular matrixmetalloproteinase-7 (MMP-7) in discriminating patients with interstitial lung diseases (ILDs) from disease control subjects. Methods: Serum levels of KL-6, SP-A, SP-D and MMP-7 were measured in both the ILD and non-ILD (NILD) groups. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic potential of these markers and laboratory indices. High-resolution computed tomography (HRCT) fibrosis scores were determined, and their correlation with the serum markers was analyzed. Results: Serum levels of KL-6 and MMP-7 were significantly elevated in the ILD group compared to the control group, while no significant differences were observed for SP-A and SP-D. ROC analysis of KL-6 demonstrated superior diagnostic accuracy, with a sensitivity of 76.36%, specificity of 91.07%, and an area under curve (AUC) of 0.902 (95%CI 0.866-0.945). These findings were consistent across an additional cohort. Correlation analysis revealed a link between KL-6 levels at initial diagnosis and HRCT fibrosis scores, indicating disease severity. Moreover, a negative correlation was found between KL-6 and pulmonary function indices, reflecting disease progression. Patients with increased 12-month HRCT fibrosis score showed higher lactate dehydrogenase (LDH) levels, with LDH exhibiting an AUC of 0.767 (95% CI: 0.520-0.927) as a predictor of progression. Conclusions: Serum KL-6 detection proves to be a valuable tool for accurately distinguishing ILDs from control subjects. While KL-6 shows a correlation with HRCT fibrosis scores and a negative association with pulmonary function indices, its predictive value for ILDs prognosis is limited. Trial registration: This study received retrospective approval from the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (institutional review board ID: TJ-IRB20210331, date: 2021.03.30).

Ultralow-cost piezoelectric sensor constructed by thermal compression bonding for long-term biomechanical signal monitoring in chronic mental disorders.

Wearable bioelectronic devices, which circumvent issues related to the large size and high cost of clinical equipment, have emerged as powerful tools for the auxiliary diagnosis and long-term monitoring of chronic psychiatric diseases. Current devices often integrate multiple intricate and expensive devices to ensure accurate diagnosis. However, their high cost and complexity hinder widespread clinical application and long-term user compliance. Herein, we developed an ultralow-cost poly(vinylidene fluoride)/zinc oxide nanofiber film-based piezoelectric sensor in a thermal compression bonding process. Our piezoelectric sensor exhibits remarkable sensitivity (13.4 mV N-1), rapid response (8 ms), and exceptional stability over 2000 compression/release cycles, all at a negligibly low fabrication cost. We demonstrate that pulse wave, blink, and speech signals can be acquired by the sensor, proposing a single biomechanical modality to monitor multiple physiological traits associated with bipolar disorder. This ultralow-cost and mass-producible piezoelectric sensor paves the way for extensive long-term monitoring and immediate feedback for bipolar disorder management.

Structural covariance in subcortical regions in multiple sclerosis and neuromyelitis optica spectrum disorders: An MRI-based study with automated brain volumetry.

PURPOSE: This study aimed to investigate the alterations of brain volumetry and associated structural covariance in subcortical regions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). MATERIALS AND METHODS: Fourty MS patients, 35 NMOSD patients and 34 healthy controls (HC) underwent 3D T1-weighted image and 3D T2 FLAIR of MRI. The volume differences in subcortical regions were compared between the MS, NMOSD, and HC groups by automated brain volumetry. Structural covariance analysis was performed with each pair of these regions to investigate the alterations of anatomical connections in MS and NMOSD compared to HC. RESULTS: Compared with HC, MS patients presented significantly smaller volume in some subcortical and infratentorial regions (P<0.05), while NMOSD patients showed no significant difference of volumetry in any of the brain regions (P>0.05), although they had no significant difference in disease duration (MS 3.95±3.73 ys; NMOSD 3.11±4.61 ys; P>0.05). In addition, the structural covariance analyses revealed synergic volume alteration in subcortical regions both in the MS and NMOSD groups. More extensive additional connections compared with HC were found in MS patients and more extensive missing connections compared with HC were found in NMOSD patients. CONCLUSION: This study revealed distinct patterns of brain structural damage and reorganization in MS and NMOSD, which could facilitate a better distinction between these two entities.

Associations Between Diffusion Dynamics and Functional Outcome in Acute and Early Subacute Ischemic Stroke.

PURPOSE: The current study aimed to investigate the associations between diffusion dynamics of ischemic lesions and clinical functional outcome of acute and early subacute stroke. MATERIAL AND METHODS: A total of 80 patients with first ever infarcts in the territory of the middle cerebral artery underwent multi-b-values diffusion-weighted imaging and diffusion kurtosis imaging. Multiple diffusion parameters were generated in postprocessing using different diffusion models. Long-term functional outcome was evaluated with modified Rankin scale (mRS) at 6 months post-stroke. Good functional outcome was defined as mRS score ≤ 2 and poor functional outcome was defined as mRS score ≥ 3. Univariate analysis was used to compare the diffusion parameters and clinical features between patients with poor and good functional outcome. Significant parameters were further analyzed for correlations with functional outcome using partial correlation. RESULTS: In univariate analyses, standard-b-values apparent diffusion coefficient (ADCst) ratio and fractional anisotropy (FA) ratio of acute stroke, ADCst ratio and mean kurtosis (MK) ratio of early subacute stroke were statistically different between patients with poor outcome and good outcome (P < 0.05). When the potential confounding factor of lesion volume was controlled, only FA ratio of acute stroke, ADCst ratio and MK ratio of early subacute stroke remained correlated with the functional outcome (P < 0.05). CONCLUSION: Diffusion dynamics are correlated with the clinical functional outcome of ischemic stroke. This correlation is independent of the effect of lesion volume and is specific to the time period between symptom onset and imaging. More effort is needed to further investigate the predictive value of diffusion-weighted imaging.

Fiber Connectivity Density in Cerebral Small-Vessel Disease Patients With Mild Cognitive Impairment and Cerebral Small-Vessel Disease Patients With Normal Cognition.

Abnormal structural connectivity of cerebral small-vessel disease (CSVD) is associated with cognitive impairment. But the different characteristics of structural connectivity have not been elucidated in early CSVD patients. The current study aimed to investigate the potential differences of structural connectivity in CSVD patients with mild cognitive impairment (MCI) and CSVD patients with normal cognition. Twenty-two CSVD patients with MCI, 34 CSVD patients with normal cognition, and 35 controls, who were age, sex, and education matched underwent diffusion tensor imaging and high resolution T1-weighted imaging. Clinical characteristics, lacunar infarct volume, white matter hyperintensity (WMH) volume, and global atrophy were quantitatively evaluated. Maps of fiber connectivity density (FiCD) were constructed and compared across groups in vertex levels. Pearson correlation was used to estimate the imaging-clinical relationships with control of general characteristics. CSVD patients with MCI had higher lesion load of WMH and lacunar infarcts, and correspondingly lower global FiCD value than CSVD patients with normal cognition (P < 0.01). Lacunar infarct (r = -0.318, P < 0.01) and WMH (r = -0.400, P < 0.01), but not global atrophy, age, or sex, were significantly correlated with the global FiCD value. CSVD patients with normal cognition showed decreased FiCD value mainly in the prefrontal areas (P < 0.01 with Monte Carlo correction). Compared with CSVD patients with normal cognition, CSVD patients with MCI showed significantly decreased FiCD value in enlarged frontal and parietal areas (P < 0.01 with Monte Carlo correction). Inter-group comparisons showed regional enhanced impairment of connectivity density in CSVD patients with MCI in the left superior frontal gyrus, the left precuneus, and the orbital part of the right inferior frontal gyrus (P < 0.01 with Monte Carlo correction). Regional FiCD value of frontal and parietal areas was associated with the cognitive function (P < 0.01). In conclusion, cognitively normal CSVD patients already have disruptions of structural connectivity. The extent and intensity of connectivity disruptions in frontal and parietal areas may underlie the mechanism of cognitive impairment in CSVD. Fiber connectivity density measurements may be helpful for quantitative description of structural cortical connectivity.

Age and anatomical location related hemodynamic changes assessed by 4D flow MRI in the carotid arteries of healthy adults.

PURPOSE: To evaluate hemodynamic changes (volume, velocity, wall shear stress, pressure gradient, and energy loss) in the common carotid artery (CCA) and internal carotid artery (ICA) of healthy adults among different ages and anatomical locations using 4D flow MRI. METHODS: Sixty-two healthy volunteers aged 20-75 years were enrolled in this study. 4D flow MRI examinations were performed for each subject and were analyzed using the CVI42 platform to generate hemodynamic parameters. Hemodynamic parameters were compared among different age groups and anatomical locations (proximal CCA, distal CCA, proximal ICA and distal CCA) using one-way ANOVA. The paired t-test was used to estimate the differences between left and right vessels. The relationship between age and hemodynamic parameters was quantified by Pearson's correlation coefficient. RESULTS: There were no differences between the left and right carotid arteries for any of the hemodynamic parameters (all p values > 0.05), so we set each vessel as an independent sample. The proximal ICA had significantly lower volume, velocity, wall shear stress, and pressure gradient values than the values determined for other locations (p < 0.05), and energy loss was similar among different locations. Wall shear stress (except in the distal ICA), velocity, pressure gradient, and energy loss decreased with age (p < 0.05). CONCLUSIONS: The multiparameter analysis of 4D flow MRI can identify age and anatomical location changes in hemodynamic parameters in the carotid arteries of healthy adults. The lower velocity, wall shear stress, and pressure gradient in the proximal ICA and the reduced trend with age may be associated with disease occurrence.

Iron concentration linked to structural connectivity in the subthalamic nucleus: implications for deep brain stimulation.

OBJECTIVE: The objective of this study was to investigate the relationship between iron and white matter connectivity in the subthalamic nucleus (STN) in patients undergoing deep brain stimulation (DBS) of the STN for treatment of Parkinson's disease. METHODS: Nine Parkinson's disease patients underwent preoperative 3T MRI imaging which included acquisition of T1-weighted anatomical images along with diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM). MR tractography was performed for the seed voxels located within the STN, and the correlations between normalized QSM values and the STN's connectivity to a set of a priori chosen regions of interest were assessed. RESULTS: A strong negative correlation was found between STN connectivity and QSM intensity for the thalamus, premotor, motor, and sensory regions, while a strong positive correlation was found for frontal, putamen, and brain stem areas. CONCLUSIONS: Quantitative susceptibility mapping not only accurately delineates the STN borders but is also able to provide functional information about the STN functional subdivisions. The observed iron-to-connectivity correlation patterns may aid in planning DBS surgery to avoid unwanted side effects associated with DBS.

Detecting normal pediatric brain development with diffusional kurtosis imaging.

PURPOSE: To characterise the pattern of change of diffusional kurtosis imaging (DKI) parameters (including kurtosis and diffusion parameters) in both white matter and gray matter in normal brain development with a large sample of subjects from term-born neonates to 14-years old children. METHODS: Two hundred and eighteen normal children (136 male, 82 female) underwent conventional magnetic resonance imaging and DKI. Regions of interest (ROIs) were placed in 7 white matter areas and 4 gray matter areas. Then the DKI-derived parameters were automatically calculated, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), radial diffusivity (Dr), mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr). The correlation between the DKI parameters and ages were analyzed using nonlinear fit, and the rate of parameter change was computed compared to the baseline value of the neonates. RESULTS: For all ROIs in the white matter and gray matter, the FA, MK, Kr, Ka values increased with age, while the MD and Dr values decreased with age. The correlations were good to excellent, which changed rapidly within the first 2 years and relatively slowly after 2 years. The Da values in peripheral white matters and some gray matter structures (caudate nucleus and putamen) decreased with age. The amplitude of kurtosis parameters variation was greater than that of the diffusion parameters in both white matter and gray matter. CONCLUSIONS: The DKI parameters correlated well with age, and kurtosis parameters showed a potential advantage in detecting the normal brain development of children.

Clinical feasibility of brain quantitative susceptibility mapping.

PURPOSE: To evaluate the quality of brain quantitative susceptibility mapping (QSM) that is fully automatically reconstructed in clinical MRI of various neurological diseases. METHODS: 393 consecutive patients in one month were recruited for this evaluation study. QSM was reconstructed using Morphology Enabled Dipole Inversion without zero reference regularization (MEDI) and using MEDI with cerebrospinal fluid automatic zero-reference regularization to generate susceptibility values (MEDI+0). Two neuroradiologists independently assessed the image quality of MEDI+0 and MEDI and image concordance between them. Lesion susceptibility values were measured in 20 cases of glioma, 21 cases of ischemic stroke and 43 multiple sclerosis (MS) cases on both MEDI+0 and MEDI images. RESULTS: The two neuroradiologists rated the MEDI+0 image qualities of the 393 cases as 351 (89.3%) and 362 (92.1%) excellent, 29 (7.4%) and 24 (6.1%) diagnostic, and 13 (3.3%) and 7 (1.8%) poor, and scored the concordances between MEDI+0 and MEDI as 364 (92.6%) and 351 (89.3%) excellent, 13 (3.3%) and 31 (7.9%) good, 14 (3.6%) and 9 (2.3%) intermediate, 2 (0.5%) and 2 (0.5%) poor, and 0 (0%) and 0 (0%) none. There was good correlation between MEDI+0 and MEDI in lesion susceptibility contrast of glioma, ischemic stroke, and MS cases (all p < 0.05). The MS lesion susceptibility time course from this patient cohort was found to be similar to the reported pattern: isointense initially for acute enhancing lesions, and hyperintense over the following years for active chronic lesions. CONCLUSION: Brain QSM images of various neurological diseases have reliable diagnostic quality in clinical MRI, with MEDI+0 providing susceptibility values automatically referenced to CSF in longitudinal and cross-center studies.