Naying He

Region-specific disturbed iron distribution in early idiopathic Parkinson's disease measured by quantitative susceptibility mapping

In Parkinsons disease (PD), iron elevation in specific brain regions as well as selective loss of dopaminergic neurons is a major pathologic feature. A reliable quantitative measure of iron deposition is a potential biomarker for PD and may contribute to the investigation of iron‐mediated PD. The primary purpose of this study is to assess iron variations in multiple deep grey matter nuclei in early PD with a novel MRI technique, quantitative susceptibility mapping (QSM). The inter‐group differences of susceptibility and R2* value in deep grey matter nuclei, namely head of caudate nucleus (CN), putamen (PUT), global pallidus (GP), substantia nigra (SN), and red nucleus (RN), and the correlations between regional iron deposition and the clinical features were explored in forty‐four early PD patients and 35 gender and age‐matched healthy controls. Susceptibility values were found to be elevated within bilateral SN and RN contralateral to the most affected limb in early PD compared with healthy controls (HCs). The finding of increased susceptibility in bilateral SN is consistent with work on a subgroup of patients at the earliest clinical detectable state (Hoehn and Yahr [1967]: Neurology 17:427–442; Stage I). However, increased R2* values were only seen within SN contralateral to the most affected limb in the PD group when compared with controls. Furthermore, bilateral SN magnetic susceptibility positively correlated with disease duration and UPDRS‐III scores in early PD. This finding supports the potential value of QSM as a non‐invasive quantitative biomarker of early PD. Hum Brain Mapp 36:4407–4420, 2015.

Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson's disease

Parkinsons disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron‐rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor‐dominant PD patients using quantitative susceptibility mapping. Forty‐three patients with PD [19 tremor dominant (TD)/24 akinetic rigidity (AR) dominant] and 48 healthy gender‐ and age‐matched controls were recruited. Multi‐echo gradient echo data were collected for each subject on a 3.0‐T MR system. Inter‐group susceptibility differences in the bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast with the AR‐dominant group, the TD group was found to have increased susceptibility in the bilateral DN when compared with healthy controls. In addition, susceptibility was positively correlated with tremor score in drug‐naive PD patients. These findings indicate that iron load within the DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR‐dominant phenotypes of PD can be differentiated on the basis of the susceptibility of the DN, at least at the group level. Copyright

Quantitative susceptibility mapping in combination with water-fat separation for simultaneous liver iron and fat fraction quantification

PurposesTo evaluate the feasibility of simultaneous quantification of liver iron concentration (LIC) and fat fraction (FF) using water-fat separation and quantitative susceptibility mapping (QSM).MethodsForty-five patients suspected of liver iron overload (LIO) were included. A volumetric interpolated breath-hold examination sequence for QSM and FF, a fat-saturated gradient echo sequence for R2*, a spin echo sequence for LIC measurements and MRS analyses for FF (FF-MRS) were performed. Magnetic susceptibility and FF were calculated using a water-fat separation method (FF-MRI). Correlation and receiver operating characteristic analyses were performed.ResultsMagnetic susceptibility showed strong correlation with LIC (rs=0.918). The optimal susceptibility cut-off values were 0.34, 0.63, 1.29 and 2.23 ppm corresponding to LIC thresholds of 1.8, 3.2, 7.0 and 15.0 mg/g dry weight. The area under the curve (AUC) were 0.948, 0.970, 1 and 1, respectively. No difference in AUC was found between susceptibility and R2* at all LIC thresholds. Correlation was found between FF-MRI and FF-MRS (R2=0.910).ConclusionsQSM has a high diagnostic performance for LIC quantification, similar to that of R2*. FF-MRI provides simultaneous fat quantification. Findings suggest QSM in combination with water-fat separation has potential value for evaluating LIO, especially in cases with coexisting steatosis.Key Points• Magnetic susceptibility showed strong correlation with LIC (rs=0.918).• QSM showed high diagnostic performance for LIC, similar to that of R2*.• Simultaneously estimated FF-MRI showed strong correlation with MR-Spectroscopy-based FF (R2=0.910).• QSM combining water-fat separation has quantitative value for LIO with coexisted steatosis.

Longitudinal atlas for normative human brain development and aging over the lifespan using quantitative susceptibility mapping

&NA; Longitudinal brain atlases play an important role in the study of human brain development and cognition. Existing atlases are mainly based on anatomical features derived from T1‐and T2‐weighted MRI. A 4D developmental quantitative susceptibility mapping (QSM) atlas may facilitate the estimation of age‐related iron changes in deep gray matter nuclei and myelin changes in white matter. To this end, group‐wise co‐registered QSM templates were generated over various age intervals from age 1–83 years old. Registration was achieved by combining both T1‐weighted and QSM images. Based on the proposed template, we created an accurate deep gray matter nuclei parcellation map (DGM map). Notably, we segmented thalamus into 5 sub‐regions, i.e. the anterior nuclei, the median nuclei, the lateral nuclei, the pulvinar and the internal medullary lamina. Furthermore, we built a “whole brain QSM parcellation map” by combining existing cortical parcellation and white‐matter atlases with the proposed DGM map. Based on the proposed QSM atlas, the segmentation accuracy of iron‐rich nuclei using QSM is significantly improved, especially for children and adolescent subjects. The age‐related progression of magnetic susceptibility in each of the deep gray matter nuclei, the hippocampus, and the amygdala was estimated. Our automated atlas‐based analysis provided a systematic confirmation of previous findings on susceptibility progression with age resulting from manual ROI drawings in deep gray matter nuclei. The susceptibility development in the hippocampus and the amygdala follow an iron accumulation model; while in the thalamus sub‐regions, the susceptibility development exhibits a variety of trends. It is envisioned that the newly developed 4D QSM atlas will serve as a template for studying brain iron deposition and myelination/demyelination in both normal aging and various brain diseases.

Quantitative susceptibility mapping (QSM) as a means to monitor cerebral hematoma treatment: QSM as a Means to Monitor Hematoma Treatment

Quantitative susceptibility mapping (QSM) offers a consistent hemorrhage volume measurement independent of imaging parameters.

Iron deposition quantification: Applications in the brain and liver: Iron Deposition Quantification

Iron has long been implicated in many neurological and other organ diseases. It is known that over and above the normal increases in iron with age, in certain diseases there is an excessive iron accumulation in the brain and liver. MRI is a noninvasive means by which to image the various structures in the brain in three dimensions and quantify iron over the volume of the object of interest. The quantification of iron can provide information about the severity of iron‐related diseases as well as quantify changes in iron for patient follow‐up and treatment monitoring. This article provides an overview of current MRI‐based methods for iron quantification, specifically for the brain and liver, including: signal intensity ratio, R2, R2* , R2′ , phase, susceptibility weighted imaging and quantitative susceptibility mapping (QSM). Although there are numerous approaches to measuring iron, R2 and R2* are currently preferred methods in imaging the liver and QSM has become the preferred approach for imaging iron in the brain.

Longitudinal data for magnetic susceptibility of normative human brain development and aging over the lifespan

The data presented in this article accompany the research article entitled “Longitudinal Atlas for Normative Human Brain Development and Aging over the Lifespan using Quantitative Susceptibility Mapping” (Zhang et al., 2018) [1]. The longitudinal evolution of magnetic susceptibility in human brain indicates critical characteristics of normal brain development and aging. In the corresponding research article, we build longitudinal QSM atlases over various age intervals using 166 healthy subjects (83F/69M) with an age range of 1–83 years old. Based on the newly built atlases, we investigate the regional evolutions of magnetic susceptibility in the brain. In this article, we report anatomical evolutions of the age-specific QSM atlases in deep gray matter nuclei and in two selected white matter fiber bundles. In addition to iron-rich brain nuclei, the evolution patterns of the magnetic susceptibility in the amygdala and hippocampus are also presented.

Imaging Parkinsonian Pathology in Substantia Nigra with MRI

Purpose of ReviewThe substantia nigra pars compacta (SNc) and its projection to the striatum undergo profound degeneration in Parkinson’s disease (PD). Literature on imaging PD-related changes in the nigrostriatal system using iron-sensitive and diffusion-sensitive MRI contrasts has been contentious, with both negative and positive results reported in each contrast. These incompatible findings may be due to the inaccurate placement of regions of interest for the SNc.Recent FindingsHistologically, SNc is characterized by the presence of melanized dopamine neurons, whereas the substantia nigra pars reticulata is characterized by high iron content. Despite this histology, previous studies have frequently relied upon iron-sensitive MRI contrast when segmenting the SNc. This is also problematic since recent work found iron-sensitive and neuromelanin-sensitive contrasts are largely non-overlapping in substantia nigra. Since neuromelanin-sensitive MRI contrast colocalizes with the melanized dopamine neurons of the SNc upon radiologic–histologic correlation, the use of neuromelanin-sensitive MRI will allow for accurate localization of SNc and better capture parkinsonian pathobiology than iron-sensitive MRI.SummaryThis article outlines iron-sensitive and diffusion-sensitive MRI contrasts, and provides an overview of neuromelanin-sensitive MRI techniques. The application of these techniques to image parkinsonian pathobiology in substantia nigra is then reviewed, with a focus on neuromelanin-sensitive imaging methods for the accurate and reproducible study of PD-related changes in SNc. These advances may help resolve current controversies surrounding MRI investigations of substantia nigra in PD and related disorders.

Shanghai cognitive intervention of mild cognitive impairment for delaying progress with longitudinal evaluation-a prospective, randomized controlled study (SIMPLE): rationale, design, and methodology

BackgroundMild cognitive impairment is an early stage of Alzheimer’s disease. Increasing evidence has indicated that cognitive training could improve cognitive abilities of MCI patients in multiple cognitive domains, making it a promising therapeutic approach for MCI. However, the effect of long-time training has not been widely explored. It is also necessary to evaluate the extent how it could reduce the convertion rate from MCI to AD.Methods/designThe SIMPLE study is a multicenter, randomized, single-blind prospective clinical trial assessing the effects of computerized cognitive training on different cognitive domains in MCI patients. It is carried out in 7 centers in China. The study population includes patients aged 50–85, and they are randomly allocated to the training or control group. The primary outcome is to compare the conversion rate of MCI within 36-month follow-up. Structural and functional MRI will be used to interpret the effect of cognitive training. The cognitive training comprises a variety of games related with cognitive domains such as attention, memory, visualspatial ability and executive function. We cautiously set 50% reduction in the rate of conversion as estimated effect. With 80–90% statistical power and 12% as the overall probability of conversion within the study period, 600–800 patients are finally required in the study. The first patent has been recruited in April 2017.DiscussionPrevious studies suggested the benefit of cognitive training for MCI, but neither long-time nor Chinese culture were investigated. The SIMPLE designs and utilizes an improved computerized cognitive training approach and assesses its effects on MCI progress. In addition, neural activities explaining the effects on cognition function changes will be revealed, which could in turn to imply more useful therapeutic approaches.Trial registrationClinicalTrials.gov Identifier: NCT03119051.

MULTI-MODEL COGNITIVE TRAINING FOR MILD COGNITIVE IMPAIRMENT PATIENTS: CLINICAL AND FUNCTIONAL NEUROIMAGING OUTCOMES FROM A PILOT STUDY

PATIENTS: CLINICAL AND FUNCTIONAL NEUROIMAGING OUTCOMES FROM A PILOT STUDY Binyin Li, Huidong Tang, Shengdi Chen, Naying He, Fuhua Yan, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China; Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China; Department of Neurology and Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China; Ruijin Hospital affiliated to Shanghai Jiaotong University, Shanghai, China. Contact e-mail: libinyin@126.com