Theoretical investigation of ultrasound-modulated Cerenkov luminescence imaging for higher-resolution imaging in turbid media

Cerenkov luminescence imaging (CLI) is an optical technique for imaging radiolabeled molecules in vivo. It has demonstrated utility in both the clinical and preclinical settings and can serve as a substitute for nuclear imaging instrumentation in some cases. However, optical scattering fundamentally limits the resolution and depth of imaging that can be achieved with this modality. In this Letter, we report the numerical results that support the potential for ultrasound-modulated Cerenkov luminescence imaging (USCLI), a new imaging modality that can mitigate optical scattering. The technique uses an acoustic field to modulate the refractive index of the medium and, thus, the intensity of Cerenkov luminescence in a spatially precise manner. This mechanism of contrast has not been reported previously. For a physiologically compatible ultrasound peak pressure of 1 MPa, ∼0.1% of the Cerenkov signal can be modulated. Furthermore, our simulations show that USCLI can overcome the scattering limit of resolution for CLI and provide higher-resolution imaging. For an¹⁸F point source centered in a 1 cm³ simulated tissue phantom with a scattering coefficient of μ_s ⁰ 10 cm⁻¹, <2 mm full width at half-maximum lateral spatial resolution is possible, a resolution three times finer than the same phantom imaged with CLI.