Noninvasive Characterization of Metabolic Changes in Ischemic Stroke Using Z-spectrum-fitted Multiparametric Chemical Exchange Saturation Transfer-weighted Magnetic Resonance Imaging

Objective This study aimed to noninvasively characterize the metabolic alterations in ischemic brain tissues using Z-spectrum-fitted multiparametric chemical exchange saturation transfer-weighted magnetic resonance imaging(CEST-MRI).Methods Three sets of Z-spectrum data with saturation power(B_(1))values of 1.5,2.5,and 3.5µT,respectively,were acquired from 17 patients with ischemic stroke.Multiple contrasts contributing to the Z-spectrum,including fitted amide proton transfer(APT_(fitted)),+2 ppm peak(CEST@2ppm),concomitantly fitted APT_(fitted) and CEST@2ppm(APT&CEST@2ppm),semisolid magnetization transfer contrast(MT),aliphatic nuclear Overhauser effect(NOE),and direct saturation of water(DSW),were fitted with 4 and 5 Lorentzian functions,respectively.The CEST metrics were compared between ischemic lesions and contralateral normal white matter(CNWM),and the correlation between the CEST metrics and the apparent diffusion coefficient(ADC)was assessed.The differences in the Z-spectrum metrics under varied B1 values were also investigated.Results Ischemic lesions showed increased APTfitted,CEST@2ppm,APT&CEST@2ppm,NOE,and DSW as well as decreased MT.APT&CEST@2ppm,MT,and DSW showed a significant correlation with ADC[APT&CEST@2ppm at the 3 B_(1) values:R=0.584/0.467/0.551;MT at the 3 B_(1) values:R=−0.717/−0.695/−0.762(4-parameter fitting),R=−0.734/−0.711/−0.785(5-parameter fitting);DSW of 4-/5-parameter fitting:R=0.794/0.811(2.5µT),R=0.800/0.790(3.5µT)].However,the asymmetric analysis of amide proton transfer(APT_(asym))could not differentiate the lesions from CNWM and showed no correlation with ADC.Furthermore,the Z-spectrum contrasts varied with B_(1).Conclusion The Z-spectrum-fitted multiparametric CEST-MRI can comprehensively detect metabolic alterations in ischemic brain tissues.

Experimental Study of Cell Migration and Functional Differentiation of Transplanted Neural Stem Cells Co-labeled with Superparamagnetic Iron Oxide and Brdu in an Ischemic Rat Model

Objective To explore the migration of transplanted neural stem cells co-labeled with superparamagnetic iron oxide （SPIO） and bromodeoxyuridine （Brdu） using the 4.7T MR system and to study the cell differentiation with immuno-histochemical method in ischemic rats. Methods Rat neural stem cells （NSCs） co-labelled with SPIO mediated by poly-L-lysine and bromodeoxyuridine （BrdU） were transplanted into the unaffected side of rat brain with middle cerebral artery occlusion （MCAO）. At weeks 1, 2, 3, 4, 5, and 6 after MCAO, migration of the labelled cells was monitored by MRI. At week 6 the rats were killed and their brain tissue was cut according to the migration site of transplanted ceils indicated by MRI and subjected to Prussian blue staining and immunohistochemical staining to observe the migration and differentiation of the transplanted NSCs. Results Three weeks after transplantation, the linear hypointensity area derived from the migration of labelled NSCs was observed by MRI in the corpus callosum adjacent to the injection site. Six weeks after the transplantation, the linear hypointensity area was moved toward the midline along the corpus callosum. MRI findings were confirmed by Prussian blue staining and immunohistochemical staining of the specimen at week 6 after the transplantation. Flourescence co-labelled immunohistochemical methods demonstrated that the transplanted NSCs could differentiate into astrocytes and neurons. Conclusion MRI can monitor the migration of SPIO-labelled NSCs after transplantation in a dynamical and non-invasive manner. NSCs transplanted into ischemic rats can differentiate into astrocytes and neurons during the process of migration.

A Comparative Study Between Tumor Blood Vessels and Dynamic Contrast-enhanced MRI for Identifying Isocitrate Dehydrogenase Gene 1(IDH1)Mutation Status in Glioma

Objective Isocitrate dehydrogenase gene(IDH)mutations are associated with tumor angiogenesis and therefore play an important role in glioma management.This study compared the performance of tumor blood vessels counted from contrast-enhanced 3D brain volume(3D-BRAVO)sequence and dynamic contrast-enhanced(DCE)MRI in differentiating IDH1 status in gliomas.Methods Forty-four glioma patients[16 with IDH1 mutant-type(IDH1-MT),28 with IDH1 wild-type(IDH1-WT)]were retrospectively analyzed.A blood vessel entering a tumor was defined as an intratumoral vessel;a blood vessel adjacent to the edge of a tumor was defined as a peritumoral vessel.Combined vessels were defined as the sum of the intratumoral and peritumoral vessels.DCE-derived metrics of tumor were normalized to the contralateral normal-appearing white matter.Results Intratumoral,peritumoral,and combined tumor blood vessels were all significantly different between IDH1-MT and IDH1-WT gliomas,and the range of area under curves(AUCs)was 0.816–0.855.For DCE-derived parameters,cerebral blood volume,cerebral blood flow,mean transit time,and volume transfer constant were significantly different between IDH1-MT and IDH1-WT gliomas,and the range of AUCs was 0.703–0.756.Combined vessels possessed the best performance for identifying IDH1 mutations in gliomas(AUC:0.855,sensitivity:0.857,specificity:0.812,P<0.001).Conclusion The number of tumor blood vessels has comparable diagnostic performance with DCE-derived parameters for differentiating IDH1 mutations and can serve as a potential imaging biomarker to reflect IDH1 mutations in gliomas.

Neurite Orientation Dispersion and Density Imaging of Rat Brain Microstructural Changes due to Middle Cerebral Artery Occlusion at a 3T MRI

The purpose of this work was to demonstrate the feasibility of neurite orientation dispersion and density imaging(NODDI)in characterizing the brain tissue microstructural changes of middle cerebral artery occlusion(MCAO)in rats at 3T MRI,and to validate NODDI metrics with histology.A multi-shell diffusion MRI protocol was performed on 11 MCAO rats and 10 control rats at different post-operation time points of 0.5,2,6,12,24 and 72 h.NODDI orientation dispersion index(ODI)and intracellular volume fraction(V_(ic))metrics were compared between MCAO group and control group.The evolution of NODDI metrics was characterized and validated by histology.Infarction was consistent with significantly increased ODI and V_(ic)in comparison to control tissues at all time points(P<0.001).Lesion ODI increased gradually from 0.5 to 72 h,while its V_(ic)showed a more complicated and fluctuated evolution.ODI and V_(ic)were significantly different between hyperacute and acute stroke periods(P<0.001).The NODDI metrics were found to be consistent with the histological findings.In conclusion,NODDI can reflect microstructural changes of brain tissues in MCAO rats at 3T MRI and the metrics are consistent with histology.This study helps to prepare NODDI for the diagnosis and management of ischemic stroke in translational research and clinical practice.

Quantitative Measurement of Cerebral Perfusion with Intravoxel Incoherent Motion in Acute Ischemia Stroke： Initial Clinical Experience

Background：Intravoxel incoherent motion （IVIM） has the potential to provide both diffusion and perfusion information without an exogenous contrast agent,its application for the brain is promising,however,feasibility studies on this are relatively scarce.The aim of this study is to assess the feasibility of IVIM perfusion in patients with acute ischemic stroke （AIS）.Methods：Patients with suspected AIS were examined by magnetic resonance imaging within 24 h of symptom onset.Fifteen patients （mean age was 68.7 ± 8.0 years） who underwent arterial spin labeling （ASL） and diffusion-weighted imaging （DWI） were identified as having AIS with ischemic penumbra were enrolled,where ischemic penumbra referred to the mismatch areas of ASL and DWI.Eleven different b-values were applied in the biexponential model.Regions of interest were selected in ischemic penumbras and contralateral normal brain regions.Fast apparent diffusion coefficients （ADCs） and ASL cerebral blood flow （CBF） were measured.The paired t-test was applied to compare ASL CBF,fast ADC,and slow ADC measurements between ischemic penumbras and contralateral normal brain regions.Linear regression and Pearson＇s correlation were used to evaluate the correlations among quantitative results.Results：The fast ADCs and ASL CBFs of ischemic penumbras were significantly lower than those of the contralateral normal brain regions （1.93 ± 0.78 μm2/ms vs.3.97 ± 2.49 μm2/ms,P =0.007;13.5 ± 4.5 ml· 100 g-1 ·min-1 vs.29.1 ± 12.7 ml·100 g-1 ·min-1,P ＜ 0.001,respectively）.No significant difference was observed in slow ADCs between ischemic penumbras and contralateral normal brain regions （0.203 ± 0.090 μm2/ms vs.0.198 ± 0.100 μm2/ms,P =0.451）.Compared with contralateral normal brain regions,both CBFs and fast ADCs decreased in ischemic penumbras while slow ADCs remained the same.A significant correlation was detected between fast ADCs and ASL CBFs （r =0.416,P ＜ 0.05）.No statistically significant correlation was observed between ASL CBFs and slow ADCs,or between fast ADCs and slow ADCs （r =0.111,P =0.558;r =0.200,P =0.289,respectively）.Conclusions：The decrease in cerebral blood perfusion primarily results in the decrease in fast ADC in ischemic penumbras;therefore,fast ADC can reflect the perfusion situation in cerebral tissues.

Rational Use of Computed Tomography for Individual Health Assessment in Asymptomatic Population： Chinese Experience

INTRODUCTIONSince computed tomography （CT） was invented and used clinically or in research, it is currently widely used in the diagnosis, staging, assessment of disease response to treatment, with clearer image quality and shorter scanning time. There are many diseases which are not easily found at an early stage with noticeable symptoms,

Frequency-specific Alterations of Large-scale Functional Brain Networks in Patients with Alzheimer＇s Disease

Background：Previous studies have indicated that the cognitive deficits in patients with Alzheimer＇s disease （AD） may be due to topological deteriorations of the brain network.However,whether the selection of a specific frequency band could impact the topological properties is still not clear.Our hypothesis is that the topological properties of AD patients are also frequency-specific.Methods：Resting state functional magnetic resonance imaging data from l0 right-handed moderate AD patients （mean age：64.3 years; mean mini mental state examination [MMSE]：18.0） and 10 age and gender-matched healthy controls （mean age：63.6 years; mean MMSE：28.2） were enrolled in this study.The global efficiency,the clustering coefficient （CC）,the characteristic path length （CpL）,and ＂small-world＂ property were calculated in a wide range of thresholds and averaged within each group,at three different frequency bands （0.01-0.06 Hz,0.06-0.11 Hz,and 0.11-0.25 Hz）.Results：At lower-frequency bands （0.01-0.06 Hz,0.06-0.11 Hz）,the global efficiency,the CC and the ＂small-world＂ properties of AD patients decreased compared to controls.While at higher-frequency bands （0.11-0.25 Hz）,the CpL was much longer,and the ＂small-world＂ property was disrupted in AD,particularly at a higher threshold.The topological properties changed with different frequency bands,suggesting the existence of disrupted global and local functional organization associated with AD.Conclusions：This study demonstrates that the topological alterations of large-scale functional brain networks inAD patients are frequency dependent,thus providing fundamental support for optimal frequency selection in future related research.