Hi Steve,
If you want to use SCPI, then yes Spike has to be running. Spike has a hidden mode, which can be activated by launching it from the command line with a special flag. The Spike user manual details this.
If you want a true headless interface, you could use the API’s which are located in our SDK. The headless APIs support only basic data acquisition such as sweeps and I/Q data. Any additional processing or operations such as markers or channel power, or etc, would need to be performed in your application.
Let me know if you have follow up questions.