Carbonic anhydrase inhibitors prevent presymptomatic capillary flow disturbances in a model of cerebral amyloidosis.

Introduction: Disturbances in microvascular flow dynamics are hypothesized to precede the symptomatic phase of Alzheimer's disease (AD). However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes.

Methods: We employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo MRI, to investigate early capillary dysfunction in Tg-SwDI mice without memory impairment.

Head holder and cranial window design for sequential magnetic resonance imaging and optical imaging in awake mice.

Medical imaging techniques are widely used in preclinical research as diagnostic tools to detect physiological abnormalities and assess the progression of neurovascular disease in animal models. Despite the wealth of imaging options in magnetic resonance imaging (MRI), interpretation of imaging-derived parameters regarding underlying tissue properties is difficult due to technical limitations or lack of parameter specificity. To address the challenge of interpretation, we present an animal preparation protocol to achieve quantitative measures from both MRI and advanced optical techniques, including laser speckle contrast imaging and two-photon microscopy, in murine models.