Correlation between iron deposition and Alzheimer's disease In vivo preliminary quantitative study with susceptibility-weighted imaging

BACKGROUND： Studies have demonstrated iron deposition in Alzheimer＇s disease （AD） patients. Therefore, quantitative measurements and tracing of iron deposition are important for early detection and treatment.OBJECTIVE： To quantitatively measure iron deposition in the brain and evaluate the relationship between iron deposition and AD using magnetic susceptibility-weighted imaging. DESIGN, TIME AND SETTING： A case-control study was performed at the Department of Radiology, Huashan Hospital of Fudan University from February to July 2008. PARTICIPANTS： A total of 20 AD patients, comprising 11 males and 9 females, with a mean age of 72.5 years （range, 51-80 years）, and 20 healthy volunteers, comprising 10 males and 10 females, with a mean age of 69.9 years （range, 55-78 years）, were selected. AD was diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association criteria.METHODS： Sagittal T2-weighted images were acquired to locate precise positions of the anterior and posterior commissures. The susceptibility-weighted magnetic resonance images were parallel to the anterior-posterior commissural line through the use of a three-dimensional gradient-echo sequence. All participants underwent measurement of corrected phase （CP） value and Mini-Mental State Examination. Pearson correlation coefficients were used to assess the association between CP values and Mini-Mental State Examination results.MAIN OUTCOME MEASURES： CP values of regions of interest in the hippocampal regions were measured on CP images.RESULTS： CP values were significantly reduced in bilateral hippocampal regions of AD patients compared with normal controls （P〈0.01）, but there were no significant differences between left and right CP values （P〉0.05）. The hippocampal mean CP value positively correlated with the Mini-Mental State Examination score in AD patients and normal controls （r= 0.57, P〈0.01）. CONCLUSION： Susceptibility-weighted imaging can be used to measure CP values to determine iron deposition in the brains of AD patients and could serve as a useful diagnostic tool for AD.

Immune microenvironment-reshaping Au@Bi_(2)Te_(3) nanoparticles for spectral computed tomography/photoacoustic imaging-guided synergetic photo/radio/immunotherapy

Radiotherapy(RT)mediated tumor immunogenicity offers an opportunity for simultaneous RT and immunotherapy via immunogenic cell death(ICD),which releases damaged-associated molecular patterns and generates“eat me”signals for the innate immune system to modulate the immunogenicity.However,tumor hypoxia significantly reduces the therapeutic efficacy of RT and hampers its mediation of ICD induction.Herein,Au@Bi_(2)Te_(3)-polyethylene glycol(PEG)was rationally constructed as theranostic nanozymes for mild photothermal therapy,tumor hypoxia modulation,and RT adjuvant cancer immunotherapy.The tumor-specific production of oxygen could not only augment the effects of RT by enhanced reactive oxygen species(ROS)generation,but also reduce hypoxia-related cytokines and downregulate programmed cell death-ligand 1(PD-L1)to unleash immune-enhancing T cells.Moreover,Au@Bi_(2)Te_(3)-PEG could act as an immune-blocking inhibitor by efficient ICD induction with the combination of mild-photothermal therapy+RT to inhibit the tumor immune escape and improve antitumor immune response.Increased amounts of CD^(4+) and CD^(8+) Tcells and elevated levels of cytokines could be observed that eventually led to effective post-medication inhibition of primary and abscopal tumors.Spectral computed tomography/photoacoustic imaging allowed noninvasive and real-time tracking of nanoparticle(NP)accumulation and oxygenation status at tumor sites.Collectively,Au@Bi_(2)Te_(3)-PEG NPs could serve as effective theranostic nanoregulators with remarkable synergistic mildphotothermal/RT/immunotherapy effects that helped reshape the immune microenvironment and had remarkable molecular imaging properties.