Cerenkov luminescence imaging (CLI) is a developing imaging modality that detects radiolabeled molecules via visible light emitted during the radioactive decay process. We used a Monte Carlo based computer simulation to quantitatively investigate CLI compared to direct detection of the ionizing radiation itself as an intraoperative imaging tool for assessment of brain tumor margins. Our brain tumor model consisted of a 1 mm spherical tumor remnant embedded up to 5 mm in depth below the surface of normal brain tissue. Tumor to background contrast ranging from 2:1 to 10:1 were considered. We quantified all decay signals (e^±, gamma photon, Cerenkov photons) reaching the brain volume surface. CLI proved to be the most sensitive method for detecting the tumor volume in both imaging and non-imaging strategies as assessed by contrast-to-noise ratio and by receiver operating characteristic output of a channelized Hotelling observer.

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 an F18 point source centered in a 1  cm³ simulated tissue phantom with a scattering coefficient of μs'=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.