In Vivo Visualization of Brain Vasculature in Alzheimer's Disease Mice by High-Frequency Micro-Doppler Imaging.

OBJECTIVE: Cerebrovascular disorders are associated with Alzheimer's disease (AD). Functional analysis of the cerebral vasculature requires an in vivo approach to visualize the blood flow in small animal brains. This paper proposes a high-frequency micro-Doppler imaging (HFµDI) technology for mapping mouse cerebral vasculature. METHODS: HFµDI used a 40-MHz transducer with an ultrafast ultrasound imaging technology that enabled in vivo visualization of the mouse brain up to 3 mm in depth; furthermore, a minimal vessel diameter of 48 µm could be determined. RESULTS: Animal experiments determined that the cortical and hippocampal vessel density in young wild-type (WT) mice was similar to that in middle-aged WT mice. However, compared with the vessel density in middle-aged WT mice, that in middle-aged mice with AD was significantly lower, particularly in the hippocampus. DISCUSSION: In vivo observation of cerebral vasculature demonstrated the effectiveness of HFµDI for the preclinical study of AD, and a potential way for human diagnosis was provided.

Ex Vivo Evaluation of Mouse Brain Elasticity Using High-Frequency Ultrasound Elastography.

OBJECTIVE: Most neurodegenerative diseases are highly linked with aging. The mechanical properties of the brain should be determined for predicting and diagnosing age-related brain diseases. A preclinical animal study is crucial for neurological disease research. However, estimation of the elasticity properties of different regions of mouse brains remains difficult because of the size of the brain. In this paper, high-frequency ultrasound elastography (HFUSE) based on shear wave imaging was proposed for mapping the stiffness of the mouse brain at different ages ex vivo. METHODS: For HFUSE, a 40-MHz ultrasound array transducer with an ultrafast ultrasound imaging system was used in this paper. The accuracy and resolution during HFUSE were determined through a mechanical testing system and by conducting phantom experiments. RESULTS: In the experiments, the error in the elastic modulus measurement was approximately 10% on average, and the axial resolution was 248 µm. Animal testing was conducted using mice that were 4 (young aged) and 11 (middle aged) months old. The elasticity distributions of the cortex and hippocampus in the mouse brains were obtained through HFUSE. CONCLUSION: The average shear moduli of the cortex and hippocampus were 3.84 and 2.33 kPa for the 4-month-old mice and 3.77 and 1.94 kPa for the 11-month-old mice, respectively. No statistical difference was observed in the cortex stiffness of mice of different ages. However, the hippocampus significantly softened with aging.

Studying Arterial Stiffness Using High-Frequency Ultrasound in Mice with Alzheimer Disease.

Alzheimer disease (AD) is an irreversible, progressive brain disorder that causes slow loss of memory and thinking skills, normally leading to death in 3-9 y. The etiology of AD is not fully understood but is widely believed to be induced by the production and deposition of amyloid-ß peptide in the brain. Recently, a correlation was discovered between amyloid-ß deposition and atherosclerosis in the cerebral arteries of postmortem brains, indicating that amyloid-ß promotes atherogenesis and that in turn atherosclerosis promotes brain amyloid-ß accumulation. However, a direct measurement of arterial stiffness for AD is lacking. In the present study, the pulse wave velocity (PWV) of the carotid artery was measured non-invasively in young (3-mo-old) and middle-aged (9-mo-old) wild-type (WT) and modeled AD mice to obtain quantitative data of arterial stiffness by using a 35-MHz high-frequency dual-element transducer. Experimental results show that the PWVs were 1.6 ± 0.5 m/s for young and 2.4 ± 0.4 m/s for middle-aged WT mice and 1.7 ± 0.4 m/s for young and 3.2 ± 0.6 m/s for middle-aged AD mice. Middle-aged groups had higher PWVs (p < 0.0001), which were more pronounced in the AD mice (p < 0.001). The differences in PWVs were not caused by arterial lumen diameter, wall thickness or contents of elastin or collagen. These results imply that AD increases the stiffness of the carotid artery and introduce ultrasound as a potential tool for AD research and diagnosis.

Acetazolamide-related life-threatening hypophosphatemia in a glaucoma patient.

Acetazolamide-related hypophosphatemia leading to cardiac arrest is extremely rare. Herein we report a 78-year-old female glaucoma patient who developed general weakness and acute respiratory failure, followed by cardiac arrest 1 day after taking acetazolamide. The patient was successfully weaned from the ventilator after correction of hypophosphatemia and fully recovered. As acetazolamide was shown to have the potential to cause a lethal side effect in stable glaucoma, the risk of hypophosphatemia should be kept in mind by ophthalmologists. An examination of serum metabolic panels may be indicated in patients at risk of hypophosphatemia.