J Biomed Opt. 2016 May 1;21(5):50502. doi: 10.1117/1.JBO.21.5.050502.
Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery
E. Spinelli 1, M.P. Schiariti 2, C.M. Grana 3, Mahila Ferrari 4, M. Cremonesi 4, F. Boschi 5
- Experimental Imaging Centre, San Raffaele Scientific Institute, Via Olgettina N. 60, Milan,20182 Italy.
- Neurosurgery unit 2, Neurological Institute C. Besta, Via Celoria 11, Milano, 20133, Italy.
- Nuclear Medicine Department, European Institute of Oncology, Via Ripamonti 435, Milan,20141, Italy.
- Medical Physics Unit, European Institute of Oncology, Via Ripamonti 435, Milan, 20141,Italy.
- Department of Computer Science, University of Verona, Strada Le Grazie 15, Verona,37134, Italy.
In this letter we presented the first example of Cerenkov luminescence imaging (CLI) and Radioluminescence imaging (RLI) of human tumor specimens.
A patient with a brain meningioma, localized in left parietal region was injected with 166 MBq of 90Y-DOTATOC the day before neurosurgery. The specimens of the tumor removed during surgery were imaged using both CLI and RLI using an optical imager prototype developed in our laboratory. The system is based on a cooled electron multiplied charge coupled device (EMCCD) coupled with an f/0.95, 17mm C-mount lens.
We showed for the first time the possibility to obtain CLI and RLI images of fresh human brain tumor specimens removed during neurosurgery.
The mechanism of Cerenkov radiation production is rather unique with respect to other and more common charged particles and matter interaction mechanisms. In this case when a charged particle travels through a dielectric medium it becomes locally polarized, and if the particle’s speed exceeds the speed of light in the medium the polarization field becomes asymmetric along the particle track producing a resultant dipole field at larger distances (see figure 1). For an electron particle traveling in water the energy threshold such that Cerenkov radiation is produced is equal to 261 keV. Muscle tissues have a slightly higher refracting index giving a lower energy threshold equal of 219 keV.
The interesting aspect is that most of the beta plus and minus emitters commonly used in nuclear medicine have end point energies greater than Cerenkov threshold in the tissues, this explains why Cerenkov luminescence imaging (CLI) is becoming a useful bridge between nuclear medicine and in vivo optical imaging1.
Recent papers using small animal optical imaging systems showed the detection of visible light when imaging alpha and gamma emitters even if the Cerenkov threshold condition is not satisfied. In order to distinguish between this imaging mechanism and CLI the term radioluminescence imaging (RLI) is commonly used. RLI can be performed with or without the use of scintillating material, however when a scintillator is used the emitted light is higher.
In our work we presented a novel application of CLI and RLI for the analysis of ex vivo fresh tumor specimens removed during neurosurgery2. The main goal of such approach is to provide a fast molecular imaging estimation of tumor uptake (almost in real time) during surgical procedures. CLI and RLI images were obtained by placing the tumor specimens in an optical imager prototype developed in our laboratory (see figure 2). The smallest achievable field of view is about 6.1 x 6.1 cm2 resulting in an image pixel size of 120 µm. The dimensions of the field of view allows the acquisition of few surgical samples simultaneously, reducing the total time needed for the imaging process. To exclude ambient light, the system is mounted on a black light-tight enclosure, in which an adjustable stage is placed for positioning the specimen.
In order to test the proposed imaging approach a patient with a brain meningioma, localized in left parietal region was injected with 166 MBq of 90Y-DOTATOC the day before surgery. The specimens of the tumor removed by the surgeon were then immediately imaged using both the CLI and RLI approach.
Figure 1. Emission of Cerenkov radiation by a beta particle with energy higher than Cerenkov threshold. In our work, the beta particle was emitted by 90Y and travels for few millimeters in the tissue.
Figure 2. Scheme of the imaging system: the CCD camera coupled with the lens is mounted on a black light-tight enclosure. An adjustable stage for the positioning of the sample is placed inside the enclosure. When RLI data were acquired a slab of 1 cm plastic scintillator was placed on top of the specimen.
The images acquired with our prototype confirm an appropriate localization of the visible Cerenkov and radioluminescence light signal within the tumor region (see figure 3).
Figure 3. On the left is shown a photographic image of the tumor specimen and on the right the corresponding CLI signal (false color). As can be seen there is a good agreement between the localization of the visible Cerenkov light signal within the tumor region (adapted from ref. 2).
To our knowledge, this is the first published experimental evidence of the possibility to detect Cerenkov and radioluminescence light from a fresh human tumor specimen removed during neurosurgery.
Importance of this work:
The approach presented in this work could provide a novel molecular imaging method to estimate tumor radiopharmaceutical uptake during surgical procedures using Cerenkov and radioluminescent light.
One of the most important precision medicine application of our method is the estimation of surgical margins using a molecular imaging guidance. We expect that the specificity of the procedure will be improved resulting in a lower tumor recurrence.
- A.E. Spinelli, F. Boschi, “Novel biomedical applications of Cerenkov radiation and radioluminescence imaging” Phys. Med. 31(2), 120–129 (2015).
- A.E. Spinelli, M.P. Schiariti, C.M. Grana, M. Ferrari, M. Cremonesi, F. Boschi, Cerenkov and Radioluminescence imaging of brain tumor specimens during neurosurgery, J. Biomed. Opt. 21 (2016).
Experimental Imaging Centre,
San Raffaele Scientific Institute,
Via Olgettina N. 60, Milan,