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Purpose: Compartment syndrome remains difficult to diagnose early in its clinical course. Pressure transducer catheters have been used to directly measure intracompartmental pressure (ICP), but this method is unreliable, with a false positive rate of 35%. We have previously used intramuscular near infrared spectroscopy to detect changes in tissue oxygen saturation (StO2) in response to increasing ICP using a novel implantable probe. However, measuring StO2 may not be sufficient to identify CS in the clinical setting. The pathophysiology of CS consists of increased ICP, leading to decreased tissue perfusion, and resulting in reduced tissue oxygenation. More clinically useful information may come from the integration of multiple data streams to aid in the diagnosis of CS. In this study, we present a novel, intramuscular probe capable of simultaneous measurement of ICP, StO2, and microvascular blood flow in a porcine model of ACS. Methods: Proof of concept for this device is demonstrated in a porcine lower extremity balloon compression model of ACS. Pressure was maintained for 20 min (short-term) or 3 h (long-term) before the balloon volume was removed. Results: In both short- and long-term experiments, as ICP increased with increasing balloon volume, the novel multimodal sensor simultaneously and reliably detected pressure elevation and corresponding reversible reductions in microvascular flow rate and tissue oxygenation. Conclusion: This novel trimodal device simultaneously measured the elevated ICP, decreased perfusion, and tissue ischemia of evolving ACS, substantiating our basic understanding of CS pathophysiology. [ABSTRACT FROM AUTHOR]