Investigating White Matter Neuroinflammation in Alzheimer Disease Using Diffusion-Based Neuroinflammation Imaging.

BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) is primarily associated with accumulations of amyloid plaques and tau tangles in gray matter, however, it is now acknowledged that neuroinflammation, particularly in white matter (WM), significantly contributes to the development and progression of AD. This study aims to investigate WM neuroinflammation in the continuum of AD and its association with AD pathologies and cognition using diffusion-based neuroinflammation imaging (NII). METHODS: This is a cross-sectional, single-center, retrospective evaluation conducted on an observational study of 310 older research participants who were enrolled in the Knight Alzheimer's Disease Research Center cohort. Hindered water ratio (HR), an index of WM neuroinflammation, was quantified by a noninvasive diffusion MRI method, NII. The alterations of NII-HR were investigated at different AD stages, classified based on CSF concentrations of ß-amyloid (Aß) 42/Aß40 for amyloid and phosphorylated tau181 (p-tau181) for tau. On the voxel and regional levels, the relationship between NII-HR and CSF markers of amyloid, tau, and neuroinflammation were examined, as well as cognition. RESULTS: This cross-sectional study included 310 participants (mean age 67.1 [±9.1] years), with 52 percent being female. Subgroups included 120 individuals (38.7%) with CSF measures of soluble triggering receptor expressed on myeloid cells 2, 80 participants (25.8%) with CSF measures of chitinase-3-like protein 1, and 110 individuals (35.5%) with longitudinal cognitive measures. The study found that cognitively normal individuals with positive CSF Aß42/Aß40 and p-tau181 had higher HR than healthy controls and those with positive CSF Aß42/Aß40 but negative p-tau181. WM tracts with elevated NII-HR in individuals with positive CSF Aß42/Aß40 and p-tau181 were primarily located in the posterior brain regions while those with elevated NII-HR in individuals with positive CSF Aß42/Aß40 and p-tau181 connected the posterior and anterior brain regions. A significant negative correlation between NII-HR and CSF Aß42/Aß40 was found in individuals with positive CSF Aß42/Aß40. Baseline NII-HR correlated with baseline cognitive composite score and predicted longitudinal cognitive decline. DISCUSSION: Those findings suggest that WM neuroinflammation undergoes alterations before the onset of AD clinical symptoms and that it interacts with amyloidosis. This highlights the potential value of noninvasive monitoring of WM neuroinflammation in AD progression and treatment.

Additive value of exposure parameters for breast cancer diagnosis in digital mammography.

OBJECTIVES: To investigate the effect of different breast lesions on exposure parameters in digital mammography and to determine whether the exposure parameters can additively improve diagnostic efficiency. METHODS: Craniocaudal view and mediolateral view full-field digital mammography images from 982 women with unilateral lesions (341 with malignant lesions, 189 with benign lesions, and 452 healthy women) obtained at Nanfang Hospital were reviewed. Differences in exposure parameters (tube voltage and load, breast thickness (BT), and average glandular dose (AGD)) between breasts were calculated. The relationships between parameter differences and lesion size were explored. A logistic regression model was used based on the AGD and BT differences, and the area under the receiver operating characteristic curve (AUC) was used to assess the performance of these parameters in differentiating malignant from benign and healthy subjects. Independently, data from 129 women (82 with malignant and 47 with benign lesions) treated at Sun Yat-sen Memorial Hospital were collected to validate the model. RESULTS: Differences in tube voltage and load, BT, and AGD between breasts were significantly greater in the malignant subjects than benign (p < 0.05) and healthy subjects (p < 0.05). The AUCs for the comparisons of malignant vs. healthy subjects, malignant vs. benign subjects, and benign vs. healthy subjects were 0.77 ± 0.02, 0.72 ± 0.02, and 0.57 ± 0.02, respectively. The model combining the exposure parameters with the BI-RADS category resulted in a higher AUC (0.910 ± 0.03) compared with physician diagnosis alone (0.820 ± 0.04) for differentiating between malignant and benign lesions. CONCLUSIONS: Exposure parameters additively improved diagnostic accuracy for breast cancer and yielded more reliable results. KEY POINTS: • Differences in kVp, mAs, BT, and AGD between breasts were significantly greater in the malignant subjects than benign and healthy subjects. • The model combining exposure parameters with the BI-RADS category resulted in a higher AUC compared with the physician's diagnosis for differentiating between malignant and benign lesions. • Exposure parameters additively improved diagnostic accuracy for breast cancer.