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Loss of function of TREM2, a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer's disease (AD). We therefore examined whether soluble TREM2 (sTREM2) concentrations in cerebrospinal fluid (CSF) were associated with reduced rates of cognitive decline and clinical progression in subjects with AD or mild cognitive impairment (MCI). We measured sTREM2 in CSF samples from 385 elderly subjects, including cognitively normal controls, individuals with MCI, and subjects with AD dementia (follow-up period: mean, 4 years; range 1.5 to 11.5 years). In subjects with AD defined by evidence of CSF Aβ1-42 (amyloid β-peptide 1 to 42; A+) and CSF p-tau181 (tau phosphorylated on amino acid residue 181; T+), higher sTREM2 concentrations in CSF at baseline were associated with attenuated decline in memory and cognition. When analyzed in clinical subgroups, an association between higher CSF sTREM2 concentrations and subsequent reduced memory decline was consistently observed in individuals with MCI or AD dementia, who were positive for CSF Aβ1-42 and CSF p-tau181 (A+T+). Regarding clinical progression, a higher ratio of CSF sTREM2 to CSF p-tau181 concentrations predicted slower conversion from cognitively normal to symptomatic stages or from MCI to AD dementia in the subjects who were positive for CSF Aβ1-42 and CSF p-tau181. These results suggest that sTREM2 is associated with attenuated cognitive and clinical decline, a finding with important implications for future clinical trials targeting the innate immune response in AD.

A substantial proportion of cognitively healthy elders (HC) show abnormally high amyloid-β (Aβ) deposition, a major pathology of Alzheimer's disease (AD). These subjects are at increased risk of Alzheimer's disease (AD) dementia, and biomarkers are needed to predict their cognitive deterioration. Here we used relevance vector regression (RVR), a pattern-recognition method, to predict concurrent cognitive decline on the basis of longitudinal gray matter (GM) changes, within two a priori, meta-analytically defined functional networks subserving episodic memory and executive function. Ninety-six HC subjects were assessed annually for three years with structural MRI and cognitive tests within the Alzheimer's Disease Neuroimaging Initiative. Presence of abnormal biomarker values of Aβ (Aβ+) were determined with cerebrospinal fluid and amyloid-PET (HC-Aβ+, n = 30; with n = 66 for normal HC-Aβ-). Using leave-one-out cross-validation, we found that in HC-Aβ+patterns of GM changes within both networks predicted decline in episodic memory (r = 0.61, p < 0.001; r = 0.40, p = 0.03), but not executive function. In HC-Aβ-, GM changes within the executive function network predicted decline in executive function (r = 0.44,p < 0.001). Previously established region-of-interest (ROI)-based predictors such as changes in hippocampal volume, within an AD-signature multi-ROI, or total GM volume were not predictive of cognitive decline in any group or cognitive domain. RVR analyses unrestricted to the a priori networks yielded compatible results with the restricted case. In conclusion, RVR-derived patterns of subtle cortical GM changes are biomarker candidates of concurrent cognitive decline in aging and subjects at risk for AD. [ABSTRACT FROM AUTHOR]

The characterization of the spatial and frequency response of acoustic detectors is important for enabling accurate optoacoustic imaging. In this work, we developed a hybrid method for the characterization of the spatially dependent response of ultrasound detectors. The method is based on the experimental determination of the receive-mode electrical impulse response (EIR) of the sensor, which is subsequently convolved with the corresponding spatial impulse response (SIR), computed numerically. The hybrid method is shown to have superior performance over purely experimental techniques in terms of accurate determination of the spatial and temporal responses of ultrasonic detectors, in high as well as low sensitivity regions of the sensor.

Purpose: Optoacoustic imaging relies on the detection of ultrasonic waves induced by laser pulse excitations to map optical absorption in biological tissue. A tomographic geometry employing a conventional ultrasound linear detector array for volumetric optoacoustic imaging is reported. The geometry is based on a translate-rotate scanning motion of the detector array, and capitalizes on the geometrical characteristics of the transducer assembly to provide a large solid angular detection aperture. A system for three-dimensional whole-body optoacoustic tomography of small animals is implemented., Methods: The detection geometry was tested using a 128-element linear array (5.0∕7.0 MHz, Acuson L7, Siemens), moved by steps with a rotation∕translation stage assembly. Translation and rotation range of 13.5 mm and 180°, respectively, were implemented. Optoacoustic emissions were induced in tissue-mimicking phantoms and ex vivo mice using a pulsed laser operating in the near-IR spectral range at 760 nm. Volumetric images were formed using a filtered backprojection algorithm., Results: The resolution of the optoacoustic tomography system was measured to be better than 130 μm in-plane and 330 μm in elevation (full width half maximum), and to be homogenous along a 15 mm diameter cross section due to the translate-rotate scanning geometry. Whole-body volumetric optoacoustic images of mice were performed ex vivo, and imaged organs and blood vessels through the intact abdominal and head regions were correlated to the mouse anatomy., Conclusions: Overall, the feasibility of three-dimensional and high-resolution whole-body optoacoustic imaging of small animal using a conventional linear array was demonstrated. Furthermore, the scanning geometry may be used for other linear arrays and is therefore expected to be of great interest for optoacoustic tomography at macroscopic and mesoscopic scale. Specifically, conventional detector arrays with higher central frequencies may be investigated.