Amide proton transfer imaging of Alzheimer's disease and Parkinson's disease

Amide proton transfer (APT) magnetic resonance imaging (MRI) is an important molecularimaging technique at the protein level in tissue. Neurodegenerative diseases have a highlikelihood of causing abnormal protein accumulation in the brain, which can be detectedby APT MRI. This article briefly introduces the principles and image processing technologyof APT MRI, and reviews the current state of research on Alzheimer's disease and Parkinson's disease using this technique. Early applications of this approach in these twoneurodegenerative diseases are encouraging, which also suggests continued technicaldevelopment and larger clinical trials to gauge the value of this technique.

Multimodality imaging using proton magnetic resonance spectroscopic imaging and ^(18)F-fluorodeoxyglucose-positron emission tomography in local prostate cancer

AIM To assess the relationship using multimodality imaging between intermediary citrate/choline metabolism as seen on proton magnetic resonance spectroscopic imaging(1H-MRSI) and glycolysis as observed on ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG-PET/CT) in prostate cancer(PCa) patients. METHODS The study included 22 patients with local PCa who were referred for endorectal magnetic resonance imaging/1HMRSI(April 2002 to July 2007) and ^(18)F-FDG-PET/CT and then underwent prostatectomy as primary or salvage treatment. Whole-mount step-section pathology was used as the standard of reference. We assessed the relationships between PET parameters [standardized uptake value(SUVmax and SUVmean)] and MRSI parameters [choline + creatine/citrate(CC/Cmax and CC/Cmean) and total number of suspicious voxels] using spearman's rank correlation, and the relationships of PET and 1H-MRSI index lesion parameters to surgical Gleason score.RESULTS Abnormal intermediary metabolism on 1H-MRSI was present in 21/22 patients, while abnormal glycolysis on ^(18)F-FDG-PET/CT was detected in only 3/22 patients. Specifically, index tumor localization rates were 0.95(95%CI: 0.77-1.00) for 1H-MRSI and 0.14(95%CI: 0.03-0.35) for ^(18)F-FDG-PET/CT. Spearman rank correlations indicated little relationship(ρ =-0.36-0.28) between 1H-MRSI parameters and ^(18)F-FDG-PET/CT parameters. Both the total number of suspicious voxels(ρ = 0.55, P = 0.0099) and the SUVmax(ρ = 0.46, P = 0.0366) correlated weakly with the Gleason score. No significant relationship was found between the CC/Cmax, CC/Cmean or SUVmean and the Gleason score(P = 0.15-0.79). CONCLUSION The concentration of intermediary metabolites detected by 1H MRSI and glycolytic flux measured ^(18)F-FDG PET show little correlation. Furthermore, only few tumors were FDG avid on PET, possibly because increased glycolysis represents a late and rather ominous event in the progression of PCa.

Amide Proton Transfer Magnetic Resonance Imaging of Alzheimer＇s Disease at 3.0 Tesla： A Preliminary Study

Background：Amide proton transfer （APT） imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging （MRI） in the field of molecular and cellular imaging.The aim of this study was to evaluate the feasibility of APT imaging to detect cerebral abnormality in patients with Alzheimer＆#39;s disease （AD） at 3.0 Tesla.Methods：Twenty AD patients （9 men and 11 women; age range,67-83 years） and 20 age-matched normal controls （11 men and 9 women; age range,63-82 years） underwent APT and traditional MRI examination on a 3.0 Tesla MRI system.The magnetic resonance ratio asymmetry （MTRasym） values at 3.5 ppm of bilateral hippocampi （Hc）,temporal white matter regions,occipital white matter regions,and cerebral peduncles were measured on oblique axial APT images.MTRasym （3.5 ppm） values of the cerebral structures between AD patients and control subjects were compared with independent samples t-test.Controlling for age,partial correlation analysis was used to investigate the associations between mini-mental state examination （MMSE） and the various MRI measures among AD patients.Results：Compared with normal controls,MTRasym （3.5 ppm） values of bilateral Hc were significantly increased in AD patients （right 1.24% ± 0.21% vs.0.83% ± 0.19%,left 1.18% ± 0.18% vs.0.80%± 0.17%,t =3.039,3.328,P =0.004,0.002,respectively）.MTRasym （3.5 ppm） values of bilateral Hc were significantly negatively correlated with MMSE （right r =-0.559,P =0.013; left r=-0.461,P =0.047）.Conclusions：Increased MTRasym （3.5 ppm） values of bilateral Hc in AD patients and its strong correlations with MMSE suggest that APT imaging could potentially provide imaging biomarkers for the noninvasive molecular diagnosis of AD.

Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors.We performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and APOE.GWAS of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI GWAS.We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI.Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was found.FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.

Simultaneous quantification of hepatic MRI-PDFF and R2* in a rabbit model with nonalcoholic fatty liver disease

Quantification of hepatic fat and iron content is important for early detection and monitoring of nonalcoholic fatty liver disease(NAFLD) patients. This study evaluated quantification efficiency of hepatic proton density fat fraction(PDFF) by MRI using NAFLD rabbits. R2* was also measured to investigate whether it correlates with fat levels in NAFLD. NAFLD rabbit model was successfully established by high fat and cholesterol diet. Rabbits underwent MRI examination for fat and iron analyses,compared with liver histological findings. MR examinations were performed on a 3.0 T MR system using multi-echo 3 D gradient recalled echo(GRE) sequence. MRI-PDFF showed significant differences between different steatosis grades with medians of3.72%(normal), 5.43%(mild), 9.11%(moderate) and 11.17%(severe), whereas this was not observed in R2*. Close correlation between MRI-PDFF and histological steatosis was observed(r=0.78, P=0.000). Hepatic iron deposit was not found in any rabbits. There was no correlation between R2* and either liver MRI-PDFF or histological steatosis. MR measuring MRI-PDFF and R2* simultaneously provides promising quantification of steatosis and iron. Rabbit NAFLD model confirmed accuracy of MRI-PDFF for liver fat quantification. R2* measurement and relationship between fat and iron of NAFLD liver need further experimental investigation.

Optimization of magnetic resonance sequences in lymph node staging of nasopharyngeal carcinoma

Background Detection rate of retropharyngeal lymph node metastasis in patients with nasopharyngeal carcinoma （NPC） needs to be improved. The purpose of this study was to compare three magnetic resonance （MR） sequences for detecting lymph nodes in patients with NPC. Methods Between July 2007 and March 2008, MR staging of pre-treated tumor was conducted on 120 patients with pathologically confirmed NPC. The outcome of three different sequences for MR NPC staging were compared： coronal short T1 inversion recovery （STIR）, axial proton density fat-suppressed （PDWI fs）, and coronal contrast enhanced fast spin echo T1 weighted fat-suppressed （CE FSE TlWl fs）. Nodal classification method （1999） was applied to count the number of retropharyngeal and cervical lymph nodes discovered by each MR sequence. Paired t tests were used for statistical analysis. Results A total of 2575 lymph nodes were found using coronal STIR sequence; 1816 lymph nodes for coronal CE FSE TIWI fs sequence and 2638 lymph nodes for axial PDWl fs sequence. Significant differences existed in the number of lymph nodes detected by axial PDWI fs and coronal CE FSE T1WI fs sequence （paired t test, P 〈0.05）, with the former sequence getting higher numbers. Statistical differences also existed between coronal STIR and coronal CE FSE TlWl fs sequence （paired ttest, P 〈0.05）, with the former sequence getting higher numbers. No significant difference was found between coronal STIR sequence and axial PDWI fs sequence （paired ttest, P 〉0.05）. Conclusions For the detection of retropharyngeal and cervical lymph nodes, coronal STIR sequence and axial PDWI fs sequence have similar performance and both sequences showed better detection than CE FSE TIWI fs sequence. Furthermore, by combining coronal STIR sequence and axial PDWI fs sequence, we can improve the detection of lymph nodes in NPC N-staging before treatment, especially for lymph nodes located in the thoracic entrance.