BACKGROUND: Mobile Stroke Units (MSU) shorten time to intravenous thrombolysis (IVT) and improve functional outcome, but they rely on computed tomography (CT) making them highly specialized and costly. Alternative technologies can potentially identify imaging-based IVT contraindications like intracranial hemorrhage (ICH) or malignancies (IM), e.g., by transcranial color-coded sonography (TCCS) and near-infrared spectroscopy (NIRS). METHODS: Using a simulation approach, we analyzed magnetic resonance imaging (MRI) scans of stroke-suspected patients within 4.5 h of symptom onset to assess TCCS and NIRS for identifying imaging-based IVT contraindications. Our study included both primary and sensitivity analyses, each employing conservative and optimistic scenarios. The primary analysis integrated clinical information from the emergency department, while the sensitivity analysis evaluated overall performance across all patients, regardless of clinical information. The conservative scenario defined TCCS detecting acute deep-brain hemorrhages or tumors >
20 mm from scalp surface or >
10 mL in volume or causing >
4 mm midline-shift, while NIRS was defined detecting them <
20 mm from scalp surface with a volume >
3.5 mL. The optimistic scenario defined TCCS detecting intracranial or subarachnoid acute/subacute hematoma or tumors >
20 mm from scalp surface or >
5 mL in volume or causing >
2 mm midline-shift, while NIRS was defined detecting them <
35 mm from the scalp surface with volume >
3.5 mL. RESULTS: We assessed 1,089 consecutive patients undergoing acute MRI, identifying 69 with imaging-based IVT contraindications, of which 40 had additional non-imaging contraindications. In the primary analysis, among those 29 patients without non-imaging-based contraindications, TCCS/NIRS would have detected 15 of 25 ICH and 3 of 4 malignant tumors in the conservative scenario. In the optimistic scenario, 18 of 25 ICH and all malignant tumors would have been detected. In the sensitivity analyses, the conservative scenario would have detected 30 of 52 ICH and 8 of 17 malignant tumors, while the optimistic scenario would have identified 37 of 52 ICH and 12 of 17 malignant tumors. CONCLUSION: While TCCS and NIRS technologies exhibit potential for identifying IVT contraindications in pre-hospital settings, comprehensive evaluation in real-world scenarios is imperative to ascertain their operational constraints.