Lingyun Zhao

Diffusion kurtosis imaging can efficiently assess the glioma grade and cellular proliferation

Conventional diffusion imaging techniques are not sufficiently accurate for evaluating glioma grade and cellular proliferation, which are critical for guiding glioma treatment. Diffusion kurtosis imaging (DKI), an advanced non-Gaussian diffusion imaging technique, has shown potential in grading glioma; however, its applications in this tumor have not been fully elucidated. In this study, DKI and diffusion weighted imaging (DWI) were performed on 74 consecutive patients with histopathologically confirmed glioma. The kurtosis and conventional diffusion metric values of the tumor were semi-automatically obtained. The relationships of these metrics with the glioma grade and Ki-67 expression were evaluated. The diagnostic efficiency of these metrics in grading was further compared. It was demonstrated that compared with the conventional diffusion metrics, the kurtosis metrics were more promising imaging markers in distinguishing high-grade from low-grade gliomas and distinguishing among grade II, III and IV gliomas; the kurtosis metrics also showed great potential in the prediction of Ki-67 expression. To our best knowledge, we are the first to reveal the ability of DKI to assess the cellular proliferation of gliomas, and to employ the semi-automatic method for the accurate measurement of gliomas. These results could have a significant impact on the diagnosis and subsequent therapy of glioma.

Investigation on positive correlation of increased brain iron deposition with cognitive impairment in Alzheimer disease by using quantitative MR R2′ mapping

Brain iron deposition has been proposed to play an important role in the pathophysiology of Alzheimer disease (AD). The aim of this study was to investigate the correlation of brain iron accumulation with the severity of cognitive impairment in patients with AD by using quantitative MR relaxation rate R2′ measurements. Fifteen patients with AD, 15 age- and sex-matched healthy controls, and 30 healthy volunteers underwent 1.5T MR multi-echo T2 mapping and T2* mapping for the measurement of transverse relaxation rate R2′ (R2′=R2*−R2). We statistically analyzed the R2′ and iron concentrations of bilateral hippocampus (HP), parietal cortex (PC), frontal white matter (FWM), putamen (PU), caudate nucleus (CN), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) of the cerebellum for the correlation with the severity of dementia. Two-tailed t-test, Student-Newman-Keuls test (ANOVA) and linear correlation test were used for statistical analysis. In 30 healthy volunteers, the R2′ values of bilateral SN, RN, PU, CN, globus pallidus (GP), TH, and FWM were measured. The correlation with the postmortem iron concentration in normal adults was analyzed in order to establish a formula on the relationship between regional R2′ and brain iron concentration. The iron concentration of regions of interest (ROI) in AD patients and controls was calculated by this formula and its correlation with the severity of AD was analyzed. Regional R2′ was positively correlated with regional brain iron concentration in normal adults (r=0.977, P<0.01). Iron concentrations in bilateral HP, PC, PU, CN, and DN of patients with AD were significantly higher than those of the controls (P<0.05); Moreover, the brain iron concentrations, especially in parietal cortex and hippocampus at the early stage of AD, were positively correlated with the severity of patients’ cognitive impairment (P<0.05). The higher the R2′ and iron concentrations were, the more severe the cognitive impairment was. Regional R2′ and iron concentration in parietal cortex and hippocampus were positively correlated with the severity of AD patients’ cognitive impairment, indicating that it may be used as a biomarker to evaluate the progression of AD.SummaryBrain iron deposition has been proposed to play an important role in the pathophysiology of Alzheimer disease (AD). The aim of this study was to investigate the correlation of brain iron accumulation with the severity of cognitive impairment in patients with AD by using quantitative MR relaxation rate R2′ measurements. Fifteen patients with AD, 15 age- and sex-matched healthy controls, and 30 healthy volunteers underwent 1.5T MR multi-echo T2 mapping and T2* mapping for the measurement of transverse relaxation rate R2′ (R2′=R2*−R2). We statistically analyzed the R2′ and iron concentrations of bilateral hippocampus (HP), parietal cortex (PC), frontal white matter (FWM), putamen (PU), caudate nucleus (CN), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) of the cerebellum for the correlation with the severity of dementia. Two-tailed t-test, Student-Newman-Keuls test (ANOVA) and linear correlation test were used for statistical analysis. In 30 healthy volunteers, the R2′ values of bilateral SN, RN, PU, CN, globus pallidus (GP), TH, and FWM were measured. The correlation with the postmortem iron concentration in normal adults was analyzed in order to establish a formula on the relationship between regional R2′ and brain iron concentration. The iron concentration of regions of interest (ROI) in AD patients and controls was calculated by this formula and its correlation with the severity of AD was analyzed. Regional R2′ was positively correlated with regional brain iron concentration in normal adults (r=0.977, P<0.01). Iron concentrations in bilateral HP, PC, PU, CN, and DN of patients with AD were significantly higher than those of the controls (P<0.05); Moreover, the brain iron concentrations, especially in parietal cortex and hippocampus at the early stage of AD, were positively correlated with the severity of patients’ cognitive impairment (P<0.05). The higher the R2′ and iron concentrations were, the more severe the cognitive impairment was. Regional R2′ and iron concentration in parietal cortex and hippocampus were positively correlated with the severity of AD patients’ cognitive impairment, indicating that it may be used as a biomarker to evaluate the progression of AD.

Intravoxel incoherent motion diffusion-weighted imaging analysis of diffusion and microperfusion in grading gliomas and comparison with arterial spin labeling for evaluation of tumor perfusion.

To determine the utility of intravoxel incoherent motion (IVIM) imaging in grading gliomas and compare IVIM perfusion metrics with arterial spin labeling (ASL)‐derived cerebral blood flow (CBF).

Voxel-Based Diffusion Tensor Imaging of an APP/PS1 Mouse Model of Alzheimer's Disease

Increasing evidence has demonstrated that white matter (WM) disruptions, due to the injury of the axon and myelin, play an important role in the pathogenesis of Alzheimer’s disease (AD). Diffusion tensor imaging (DTI) is a sensitive modality to evaluate the WM integrity in both AD patients and animal models. In this study, an advanced DTI modality, employing a 7.0-T magnetic resonance imaging system, was used to analyze WM changes across the whole brain of an amyloid precursor protein/presenilin 1 (APP/PS1) mouse model. A voxel-based analysis was used to compare the quantitative DTI parameters automatically in both APP/PS1 mice (n = 9) and wild-type (WT) controls (n = 9). After DTI examination, the ultrastructure analysis was compared with DTI findings. Compared with WT controls, gray matter (GM) areas in APP/PS1 mice such as the cingulate cortex and the striatum showed significant fractional anisotropy (FA) and axial diffusivity (DA) increase, while the thalamus only showed a significant FA increase (p < 0.01). Similarly, a significant mean diffusivity, DA, and radial diffusivity increase was observed in the bilateral neocortex (p < 0.01). The left hippocampus only showed significant FA increase in APP/PS1 mice (p < 0.01). The changes in WM regions were detected in the forceps minor of the corpus callosum, the anterior part of the anterior commissure, and the internal capsule, with a significant FA or DA increase (p < 0.01). Abnormalities derived from diffusion measurements were in-line with the ultrastructure findings, including extensive pathological damage of the neurons, neutrophils, and vessels. In conclusion, voxel-based diffusion tensor imaging can detect diffusion alterations not only in GM but also in WM areas in AD models, reflecting the extensive pathological changes of AD.

The temporal evolution of diffusional kurtosis imaging in an experimental middle cerebral artery occlusion (MCAO) model.

PURPOSE Diffusional kurtosis imaging (DKI), as a non-Gaussian diffusion model, has been applied in human and animal studies of ischemic stroke. This study aimed to intensively characterize the temporal evolution of DKI-derived variables in an experimental middle cerebral artery occlusion (MCAO) model, and to explore its potential application in ischemic stroke. MATERIALS AND METHODS Eleven MCAO rats and ten control rats underwent DKI and diffusion weighted imaging (DWI) scans, at different time points of 0.5, 2, 6, 12, 24 and 72h after operation respectively. The infarct area in DKI- and DWI-derived variables was compared among different time points, and between different groups [INFARCTION, MIRROR, CONTROL-R (right side of the control group, the same side as in the infarction group), CONTROL-L (left side of the control group)] using repeated measures analysis of variance (ANOVA). The percent changes from normal to that in ischemic tissues and histology were also evaluated. RESULTS In the infarct region, from 0.5 to 72h, MK, K∥, K⊥ demonstrated irregular high signal, whereas relative homogeneous low signals were revealed by MD, D∥, D⊥ and ADC. Compared with the MIRROR and CONTROL-R group, MK, K∥, K⊥ in the infarcted area increased aggressively which peaked at 12h and gradually decreased; MD, D∥, D⊥ and ADC decreased gradually until 12h and then began to increase gradually; FA decreased rapidly from 0.5 to 72h. MD, D∥ and ADC were significantly different between Mirror and CONTROL-L group (P<0.05). CONCLUSION DKI can provide more detailed information to describe ischemic lesion, and has great potential application in ischemic stroke.

Comparative study of DSC-PWI and 3D-ASL in ischemic stroke patients

The purpose of this study was to quantitatively analyze the relationship between three dimensional arterial spin labeling (3D-ASL) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) in ischemic stroke patients. Thirty patients with ischemic stroke were included in this study. All subjects underwent routine magnetic resonance imaging scanning, diffusion weighted imaging (DWI), magnetic resonance angiography (MRA), 3D-ASL and DSC-PWI on a 3.0T MR scanner. Regions of interest (ROIs) were drawn on the cerebral blood flow (CBF) maps (derived from ASL) and multi-parametric DSC perfusion maps, and then, the absolute and relative values of ASL-CBF, DSC-derived CBF, and DSC-derived mean transit time (MTT) were calculated. The relationships between ASL and DSC parameters were analyzed using Pearson’s correlation analysis. Receiver operative characteristic (ROC) curves were performed to define the thresholds of relative value of ASL-CBF (rASL) that could best predict DSC-CBF reduction and MTT prolongation. Relative ASL better correlated with CBF and MTT in the anterior circulation with the Pearson correlation coefficients (R) values being 0.611 (P<0.001) and–0.610 (P<0.001) respectively. ROC curves demonstrated that when rASL ≤0.585, the sensitivity, specificity and accuracy for predicting ROIs with rCBF<0.9 were 92.3%, 63.6% and 76.6% respectively. When rASL ≤0.952, the sensitivity, specificity and accuracy for predicting ROIs rMTT>1.0 were 75.7%, 89.2% and 87.8% respectively. ASL-CBF map has better linear correlations with DSC-derived parameters (DSC-CBF and MTT) in anterior circulation in ischemic stroke patients. Additionally, when rASL is lower than 0.585, it could predict DSC-CBF decrease with moderate accuracy. If rASL values range from 0.585 to 0.952, we just speculate the prolonged MTT.The purpose of this study was to quantitatively analyze the relationship between three dimensional arterial spin labeling (3D-ASL) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) in ischemic stroke patients. Thirty patients with ischemic stroke were included in this study. All subjects underwent routine magnetic resonance imaging scanning, diffusion weighted imaging (DWI), magnetic resonance angiography (MRA), 3D-ASL and DSC-PWI on a 3.0T MR scanner. Regions of interest (ROIs) were drawn on the cerebral blood flow (CBF) maps (derived from ASL) and multi-parametric DSC perfusion maps, and then, the absolute and relative values of ASL-CBF, DSC-derived CBF, and DSC-derived mean transit time (MTT) were calculated. The relationships between ASL and DSC parameters were analyzed using Pearson’s correlation analysis. Receiver operative characteristic (ROC) curves were performed to define the thresholds of relative value of ASL-CBF (rASL) that could best predict DSC-CBF reduction and MTT prolongation. Relative ASL better correlated with CBF and MTT in the anterior circulation with the Pearson correlation coefficients (R) values being 0.611 (P<0.001) and–0.610 (P<0.001) respectively. ROC curves demonstrated that when rASL ≤0.585, the sensitivity, specificity and accuracy for predicting ROIs with rCBF<0.9 were 92.3%, 63.6% and 76.6% respectively. When rASL ≤0.952, the sensitivity, specificity and accuracy for predicting ROIs rMTT>1.0 were 75.7%, 89.2% and 87.8% respectively. ASL-CBF map has better linear correlations with DSC-derived parameters (DSC-CBF and MTT) in anterior circulation in ischemic stroke patients. Additionally, when rASL is lower than 0.585, it could predict DSC-CBF decrease with moderate accuracy. If rASL values range from 0.585 to 0.952, we just speculate the prolonged MTT.

Amide Proton Transfer Imaging Allows Detection of Glioma Grades and Tumor Proliferation: Comparison with Ki-67 Expression and Proton MR Spectroscopy Imaging

Amide proton transfer–weighted imaging (APTWI) is a novel molecular MR imaging technique developed to detect and quantitatively visualize endogenous proteins and peptides. APTWI is usually reported in terms of asymmetry in the magnetization transfer ratio at 3.5 ppm. This study included 42 patients with low-grade (n = 28) or high-grade (n = 14) glioma, all of whom underwent conventional MR imaging, proton MR spectroscopy imaging, and amide proton transfer–weighted imaging on the same 3T scanner within 2 weeks before surgery. The asymmetric magnetization transfer ratio at 3.5 ppm values measured by different readers showed good concordance and were significantly higher in high-grade gliomas than in low-grade gliomas, with sensitivity and specificity values of 92.9% and 71.4%, respectively, at a cutoff value of 2.93%. The asymmetric magnetization transfer ratio at 3.5 ppm may serve as a potential biomarker not only for assessing proliferation, but also for predicting histopathologic grades in gliomas. BACKGROUND AND PURPOSE: Prognosis in glioma depends strongly on tumor grade and proliferation. In this prospective study of patients with untreated primary cerebral gliomas, we investigated whether amide proton transfer–weighted imaging could reveal tumor proliferation and reliably distinguish low-grade from high-grade gliomas compared with Ki-67 expression and proton MR spectroscopy imaging. MATERIALS AND METHODS: This study included 42 patients with low-grade (n = 28) or high-grade (n = 14) glioma, all of whom underwent conventional MR imaging, proton MR spectroscopy imaging, and amide proton transfer–weighted imaging on the same 3T scanner within 2 weeks before surgery. We assessed metabolites of choline and N-acetylaspartate from proton MR spectroscopy imaging and the asymmetric magnetization transfer ratio at 3.5 ppm from amide proton transfer–weighted imaging and compared them with histopathologic grade and immunohistochemical expression of the proliferation marker Ki-67 in the resected specimens. RESULTS: The asymmetric magnetization transfer ratio at 3.5 ppm values measured by different readers showed good concordance and were significantly higher in high-grade gliomas than in low-grade gliomas (3.61% ± 0.155 versus 2.64% ± 0.185, P = .0016), with sensitivity and specificity values of 92.9% and 71.4%, respectively, at a cutoff value of 2.93%. The asymmetric magnetization transfer ratio at 3.5 ppm values correlated with tumor grade (r = 0.506, P = .0006) and Ki-67 labeling index (r = 0.502, P = .002). For all patients, the asymmetric magnetization transfer ratio at 3.5 ppm correlated positively with choline (r = 0.43, P = .009) and choline/N-acetylaspartate ratio (r = 0.42, P = .01) and negatively with N-acetylaspartate (r = −0.455, P = .005). These correlations held for patients with low-grade gliomas versus those with high-grade gliomas, but the correlation coefficients were higher in high-grade gliomas (choline: r = 0.547, P = .053; N-acetylaspartate: r = −0.644, P = .017; choline/N-acetylaspartate: r = 0.583, P = .036). CONCLUSIONS: The asymmetric magnetization transfer ratio at 3.5 ppm may serve as a potential biomarker not only for assessing proliferation, but also for predicting histopathologic grades in gliomas.

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

ObjectivesUsing 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.MethodsSeventeen 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).ResultsAPT 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.ConclusionsAPT and MT could provide independent and supplementary information for the comprehensive assessment of molecular and structural changes due to brain tumor cancerogenesis.Key Points• MTRasym(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.