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Multi-parametric photoacoustic microscopy (PAM) has emerged as a promising new technique for high-resolution quantification of hemodynamics and oxygen metabolism in the mouse brain. In this work, we have extended the scope of multi-parametric PAM to longitudinal, cortex-wide, awake-brain imaging with the use of a long-lifetime (24 weeks), wide-field (5 × 7 mm 2 ), light-weight (2 g), dual-transparency ( i.e., light and ultrasound) cranial window. Cerebrovascular responses to the window installation were examined in vivo, showing a complete recovery in 18 days. In the 22-week monitoring after the recovery, no dura thickening, skull regrowth, or changes in cerebrovascular structure and function were observed. The promise of this technique was demonstrated by monitoring vascular and metabolic responses of the awake mouse brain to ischemic stroke throughout the acute, subacute, and chronic stages. Side-by-side comparison of the responses in the ipsilateral (injury) and contralateral (control) cortices shows that despite an early recovery of cerebral blood flow and an increase in microvessel density, a long-lasting deficit in cerebral oxygen metabolism was observed throughout the chronic stage in the injured cortex, part of which proceeded to infarction. This longitudinal, functional-metabolic imaging technique opens new opportunities to study the chronic progression and therapeutic responses of neurovascular diseases.
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Peritubular Capillary Oxygen Consumption in Sepsis-Induced AKI: Multi-Parametric Photoacoustic Microscopy
Understanding and measuring parameters responsible for the pathogenesis of sepsis-induced AKI (SI-AKI) is critical in developing therapies. Blood flow to the kidney is heterogeneous, partly due to the existence of dynamic networks of capillaries in various regions, responding differentially to oxygen demand in cortex versus medulla. High energy demand regions, especially the outer medulla, are susceptible to hypoxia and subject to damage during SI-AKI. Proximal tubule epithelial cells in the cortex and the outer medulla can also undergo metabolic reprogramming during SI-AKI to maintain basal physiological status and to avoid potential damage. Current data on the assessment of renal hemodynamics and oxygen metabolism during sepsis is limited. Preclinical and clinical studies show changes in renal hemodynamics associated with SI-AKI, and in clinical settings, interventions to manage renal hemodynamics seem to help improve disease outcomes in some cases. Lack of proper tools to assess temporospatial changes in peritubular blood flow and tissue oxygen metabolism is a barrier to our ability to understand microcirculatory dynamics and oxygen consumption and their role in the pathogenesis of SI-AKI. Current tools to assess renal oxygenation are limited in their usability as these cannot perform continuous simultaneous measurement of renal hemodynamics and oxygen metabolism. Multi-parametric photo-acoustic microscopy (PAM) is a new tool that can measure real-time changes in microhemodynamics and oxygen metabolism. Use of multi-parametric PAM in combination with advanced intravital imaging techniques has the potential to understand the contribution of microhemodynamic and tissue oxygenation alterations to SI-AKI.
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- Award ID(s):
- 2023988
- PAR ID:
- 10216026
- Date Published:
- Journal Name:
- Nephron
- Volume:
- 144
- Issue:
- 12
- ISSN:
- 1660-8151
- Page Range / eLocation ID:
- 621 to 625
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1159/000511167
