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Polycrystalline para-terphenyl scintillator adopted in a $beta^-$ detecting probe for radio-guided surgery

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 نشر من قبل Elena Solfaroli Camillocci
 تاريخ النشر 2015
  مجال البحث فيزياء
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A radio-guided surgery technique exploiting $beta^-$ emitters is under development. It aims at a higher target-to-background activity ratio implying both a smaller radiopharmaceutical activity and the possibility of extending the technique to cases with a large uptake of surrounding healthy organs. Such technique requires a dedicated intraoperative probe detecting $beta^-$ radiation. A first prototype has been developed relying on the low density and high light yield of the diphenylbutadiene doped para-therphenyl organic scintillator. The scintillation light produced in a cylindrical crystal, 5 mm in diameter and 3 mm in height, is guided to a photo-multiplier tube by optical fibres. The custom readout electronics is designed to optimize its usage in terms of feedback to the surgeon, portability and remote monitoring of the signal. Tests show that with a radiotracer activity comparable to those administered for diagnostic purposes the developed probe can detect a 0.1 ml cancerous residual of meningioma in a few seconds.



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The development of the $beta^-$ based radio-guided surgery aims to extend the technique to those tumours where surgery is the only possible treatment and the assessment of the resection would most profit from the low background around the lesion, as for brain tumours. Feasibility studies on meningioma, glioma, and neuroendocrine tumors already estimated the potentiality of this new treatment. To validate the technique, prototypes of the intraoperative probe required by the technique to detect $beta^-$ radiation have been developed. This paper discusses the design details of the device and the tests performed in laboratory. In such tests particular care has to be taken to reproduce the surgical field conditions. The innovative technique to produce specific phantoms and the dedicated testing protocols is described in detail.
Organic scintillators are often chosen as radiation detectors for their fast decay time and their low Z, while inorganic ones are used when high light ields are required. In this paper we show that a para-terphenyl based detector has a blend of prope rties of the two categories that can be optimal for energy and position measurements of low energy charged particles. On 0.1% diphenylbutadiene doped para-terphenyl samples we measure a light yield 3.5+-0.2 times larger than a typical organic scintillator (EJ-200), and a rejection power for 660 keV photons, with respect to electrons of the same energy, ranging between 3-11%, depending on the signal threshold. We also measure a light attenuation length = 4.73+-0.06 mm and we demonstrate that, with the measurements performed in this paper, a simulation based on FLUKA can properly reproduce the measured spectra.
The $beta^-$ based radio-guided surgery overcomes the corresponding $gamma$ technique in case the background from healthy tissues is relevant. It can be used only in case a radio-tracer marked with $^{90}$Y is available since the current probe protot ype was optimized for the emission spectrum of this radio-nuclide. Here we study, with a set of laboratory tests and simulations, the prototype capability in case a different radio-nuclide is chosen among those used in nuclear medicine. As a result we estimate the probe efficiency on electrons and photons as a function of energy and we evaluate the feasibility of a radio-guided surgery exploiting the selected radio-nuclides. We conclude that requiring a 0.1~ml residue to be detected within 1~s by administering 3~MBq/Kg of radio-isotope, the current probe prototype would yield a significant signal in a vast range of values of SUV and TNR in case $^{31}$Si,$^{32}$P, $^{97}$Zr, and $^{188}$Re are used. Conversely, a tuning of the detector would be needed to efficiency use $^{83}$Br, $^{133}$I, and $^{153}$Sm, although they could already be used in case of high SUV or TNR values. Finally, $^{18}$F,$^{67}$Cu, $^{131}$I, and $^{177}$Lu are not useable for radio-guided surgery with the current probe design.
The recent interest in beta- radionuclides for radio-guided surgery derives from the feature of the beta radiation to release energy in few millimeters of tissue. Such feature can be used to locate residual tumors with a probe located in its immediat e vicinity, determining the resection margins with an accuracy of millimeters. The drawback of this technique is that it does not allow to identify tumors hidden in more than few mm of tissue. Conversely, the bremsstrahlung X-rays emitted by the interaction of the beta- radiation with the nuclei of the tissue are relatively penetrating. To complement the beta- probes, we have therefore developed a detector based on cadmium telluride, an X-ray detector with a high quantum efficiency working at room temperature. We measured the secondary emission of bremsstrahlung photons in a target of Polymethylmethacrylate (PMMA) with a density similar to living tissue. The results show that this device allows to detect a 1 ml residual or lymph-node with an activity of 1 kBq hidden under a layer of 10 mm of PMMA with a 3:1 signal to noise, i.e. with a five sigma discrimination in less than 5 s.
Purpose: A radio-guided surgery technique with beta- -emitting radio-tracers was suggested to overcome the effect of the large penetration of gamma radiation. The feasibility studies in the case of brain tumors and abdominal neuro-endocrine tumors we re based on simulations starting from PET images with several underlying assumptions. This paper reports, as proof-of-principle of this technique, an ex-vivo test on a meningioma patient. This test allowed to validate the whole chain, from the evaluation of the SUV of the tumor, to the assumptions on the bio-distribution and the signal detection. Methods: A patient affected by meningioma was administered 300 MBq of 90Y-DOTATOC. Several samples extracted from the meningioma and the nearby Dura Mater were analyzed with a beta- probe designed specifically for this radio-guided surgery technique. The observed signals were compared both with the evaluation from the histology and with the Monte Carlo simulation. Results: we obtained a large signal on the bulk tumor (105 cps) and a significant signal on residuals of $sim$0.2 ml (28 cps). We also show that simulations predict correctly the observed yields and this allows us to estimate that the healthy tissues would return negligible signals (~1 cps). This test also demonstrated that the exposure of the medical staff is negligible and that among the biological wastes only urine has a significant activity. Conclusions: This proof-of-principle test on a patient assessed that the technique is feasible with negligible background to medical personnel and confirmed that the expectations obtained with Monte Carlo simulations starting from diagnostic PET images are correct.
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