Optical imaging of Cerenkov light generation from positron-emitting radiotracers

Department of Imaging Sciences, Millennium Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
Physics in Medicine and Biology (Impact Factor: 2.76). 09/2009; 54(16):N355-65. DOI: 10.1088/0031-9155/54/16/N01
Source: PubMed


Radiotracers labeled with high-energy positron emitters, such as those commonly used for positron emission tomography studies, emit visible light immediately following decay in a medium. This phenomenon, not previously described for these imaging tracers, is consistent with Cerenkov radiation and has several potential applications, especially for in vivo molecular imaging studies. Herein we detail a new molecular imaging tool, Cerenkov Luminescence Imaging, the experiments conducted that support our interpretation of the source of the signal, and proof-of-concept in vivo studies that set the foundation for future application of this new method.

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Available from: Changqing Li, Dec 23, 2013
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    • "In recent years there has been a growing interest in biophotonic applications of Cherenkov radiation, a form of light emission that occurs when a charged particle exceeds the local speed of light in a dielectric medium (Čerenkov 1937). To date, these applications have included small animal imaging and tomography of radionuclide distributions and kinetics (Robertson et al 2009, Hu et al 2010, Li et al 2010, Spinelli et al 2010, Boschi et al 2011, Mitchell et al 2011), clinical imaging of 18 F-FDG in human patients (Holland et al 2011, Thorek et al 2014), intraoperative imaging (Holland et al 2011, Liu et al 2012, Thorek et al 2012, Carpenter et al 2014), as well as dosimetric imaging during external beam radiation therapy and brachytherapy (Glaser et al 2013a, 2013b, 2013d, 2014, Zhang et al 2013a, 2013b, 2013c, Jarvis et al 2014, Lohrmann et al 2015). While all of these studies have appreciated the inherently weak intensity of this form of light emission, there have been limited attempts at absolute quantiication of the light luence of Cherenkov radiation for each of these applications. "
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    ABSTRACT: Cherenkov radiation has recently emerged as an interesting phenomenon for a number of applications in the biomedical sciences. Its unique properties, including broadband emission spectrum, spectral weight in the ultraviolet and blue wavebands, and local generation of light within a given tissue, have made it an attractive new source of light within tissue for molecular imaging and phototherapy applications. While several studies have investigated the total Cherenkov light yield from radionuclides in units of [photons/decay], further consideration of the light propagation in tissue is necessary to fully consider the utility of this signal in vivo. Therefore, to help further guide the development of this novel field, quantitative estimates of the light fluence rate of Cherenkov radiation from both radionuclides and radiotherapy beams in a biological tissue are presented for the first time. Using Monte Carlo simulations, these values were found to be on the order of 0.01–1 nW cm−2 per MBq g−1 for radionuclides, and 1–100 μW cm−2 per Gy s−1 for external radiotherapy beams, dependent on the given waveband, optical properties, and radiation source. For phototherapy applications, the total light fluence was found to be on the order of nJ cm−2 for radionuclides, and mJ cm−2 for radiotherapy beams. The results indicate that diagnostic potential is reasonable for Cherenkov excitation of molecular probes, but phototherapy may remain elusive at such exceedingly low fluence values. The results of this study are publicly available for distribution online at
    Physics in Medicine and Biology 09/2015; 60(17). DOI:10.1088/0031-9155/60/17/6701 · 2.76 Impact Factor
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    • "Cherenkov detector are used for particle identification in high-energy physics experiments [4] [5] [6] [7] [8], and for cosmic radiation measurements in astrophysics [9] [10]; It is serving as the basis of novel acceleration methods [11], and even as an unusual imaging tool in biology [12] [13]. The fundamental nature of ČR has led to an incredible amount of research that continues to this day, as novel Čerenkov-related effects are being found in previously unexplored settings and even in modern nanostructures, including photonic crystals [14] and metamaterials [15]. "
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    ABSTRACT: We show that the well-established \v{C}erenkov Effect contains new phenomena arising directly from the quantum nature of the charged particles. These include large deviations from the classically-expected radiation intensity and angle. Most importantly, we find that the traditional Cerenkov angle splits, confining the emitted radiation into two distinctive cones into which two photonic shock waves are emitted. Interestingly, one of the two shockwaves can move on a backward cone, which is otherwise considered impossible for \v{C}erenkov Radiaiton in ordinary materials. Moreover, for specific values of the particle momentum, we predict an upper frequency cutoff in the photon emission. Surprisingly, for this extremum frequency we find a diverging rate of photon emission, implying this is a new resonant light-matter interaction. Some of these new effects cannot be found without the full quantum derivation. Importantly, our findings are observable for electron beams with realistic parameters, offering new applications including coherent x-ray sources and open a new realm for \v{C}erenkov detectors.
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    • "Biol. 59 (2014) 5317 et al 2011, Spinelli and Boschi 2012, 2014, Glaser et al 2013a, 2013d, Zhang et al 2013a, 2013c), and tissues which have been injected with radiotracers (Robertson et al 2009, Hu et al 2010). The spectrum of Cherenkov emission is highly weighted to the ultraviolet/blue spectral region. "
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    ABSTRACT: Megavoltage radiation beams used in External Beam Radiotherapy (EBRT) generate Cherenkov light emission in tissues and equivalent phantoms. This optical emission was utilized to excite an oxygen-sensitive phosphorescent probe, PtG4, which has been developed specifically for NIR lifetime-based sensing of the partial pressure of oxygen (pO2). Phosphorescence emission, at different time points with respect to the excitation pulse, was acquired by an intensifier-gated CCD camera synchronized with radiation pulses delivered by a medical linear accelerator. The pO2 distribution was tomographically recovered in a tissue-equivalent phantom during EBRT with multiple beams targeted from different angles at a tumor-like anomaly. The reconstructions were tested in two different phantoms that have fully oxygenated background, to compare a fully oxygenated and a fully deoxygenated inclusion. To simulate a realistic situation of EBRT, where the size and location of the tumor is well known, spatial information of a prescribed region was utilized in the recovery estimation. The phantom results show that region-averaged pO2 values were recovered successfully, differentiating aerated and deoxygenated inclusions. Finally, a simulation study was performed showing that pO2 in human brain tumors can be measured to within 15 mmHg for edge depths less than 10–20 mm using the Cherenkov Excited Phosphorescence Oxygen imaging (CEPhOx) method and PtG4 as a probe. This technique could allow non-invasive monitoring of pO2 in tumors during the normal process of EBRT, where beams are generally delivered from multiple angles or arcs during each treatment fraction.
    Physics in Medicine and Biology 08/2014; 59(18):5317. DOI:10.1088/0031-9155/59/18/5317 · 2.76 Impact Factor
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