# Assessment of retinal and sublingual microcirculation as surrogate biomarkers for cerebral microcirculatory dynamics

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $205,000

## Abstract

Abstract/Project Summary
Impairment of microcirculatory blood flow has been implicated as a pivotal pathophysiologic event in acutely
critically ill patients. As the brain is particularly sensitive to insufficient perfusion, cognitive impairment,
particularly in the elderly, can prolong the recovery period and significantly impact the ability to live independently.
Resuscitation or perfusion management in critically ill patients is primarily guided by macrocirculatory
assessment (i.e., arterial blood pressure (ABP)) with little consideration of the microcirculation, as
microcirculatory parameters are technically difficult to assess. Such practice operates under the assumption that
resuscitation aimed at correcting macro-hemodynamic variables is also effective in correcting microcirculatory
perfusion and oxygen delivery to the brain tissue, a relationship termed hemodynamic coherence. However,
recent studies in pathophysiologic states (e.g., sepsis, shock) strongly suggest that microvascular perfusion is
not restored despite the optimization of macrocirculatory parameters. Thus, there is an urgent need to learn
what governs cerebral microcirculatory flow, dissect conditions that compromise hemodynamic coherence and
define effective microcirculation resuscitation targets. Further, while research tools exist, there is no commonly
accepted technique which can measure microcirculation through the intact skull. Therefore, it is essential to
identify more accessible microcirculatory beds (e.g., sublingual, retinal) which may serve as surrogates for
cerebral microcirculatory flow. Characterizing surrogate microcirculations as flow-biomarkers is a critical step
towards practical clinical implementation of microcirculatory targets for resuscitation. Our long-term goal is to
develop effective strategies to enhance microcirculatory perfusion and effective oxygen delivery to the brain
under critical clinical conditions that require resuscitation. The primary goals of this proposal are to a) investigate
the role of the microcirculation in cerebral hemodynamic coherence in the gyrencephalic brain and b)
characterize effective cerebral microcirculation proxies that can be developed as non-invasive surrogate
biomarkers for bedside clinical management. We will manipulate cardiovascular physiology reflecting common
intraoperative scenarios (i.e., hemorrhagic hypotension) and hypothesize that current resuscitation strategies, in
particular the use of high concentrations of vasopressors, do not restore microvascular function but lead to long-
lasting cerebral microvascular constriction and result in brain injury. In Aim 1 we will assess cerebral
hemodynamic coherence and oxygen delivery during induced hemorrhagic hypotension and resuscitation using
multimodal microvascular imaging techniques. In Aim 2 we will determine the relationship between a) sublingual
and b) retinal and cerebral microcirculatory dynamics and investigate their potential as surrogate biomarkers f...

## Key facts

- **NIH application ID:** 10918302
- **Project number:** 5R21NS135307-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Ulrike Hoffmann
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $205,000
- **Award type:** 5
- **Project period:** 2023-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918302

## Citation

> US National Institutes of Health, RePORTER application 10918302, Assessment of retinal and sublingual microcirculation as surrogate biomarkers for cerebral microcirculatory dynamics (5R21NS135307-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10918302. Licensed CC0.

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