This paper presented the feasibility of locally applied portable spectrometers to detect and characterise the presence of anomalies or extravasation events. As far as the authors are aware, this is the first time that, by analysing the signal relating to the first 10 minutes of radiopharmaceutical administration monitored with two conventional portable spectrometers, a method to correct the SUV value in case of extravasation is proposed. The described metrics could be applied to predict SUV correction factors before PET imaging acquisition. Furthermore, the method indicates the possibility of estimating the presence of extravasation and the need for SUV correction also using a single detector placed on the injection arm.
A commercial device has been proposed on the market, the LARA system, capable of recognizing the presence of extravasation, or abnormal retention, monitoring the patient during the administration phase of the radiopharmaceutical over 40–60 minutes. Since Lara sensors record the relative level of radiotracer in the areas of interest during and after administration, they provide clinicians with evidence of the presence of an event of extravasation. Similar information can also be obtained with our method which does not use a dedicated commercial system but uses portable spectrometers, which are present and already used in Nuclear Medicine services. Unlike the publications in the literature that use the LARA system for monitoring [13, 17, 19, 20], we have acquired DR values over a time interval of 10 minutes instead of 40–60 minutes. This choice is related to the results obtained in previous works present in the literature that use the LARA device. In each of these works, the acquisitions were made over a time interval between 40 and 60 minutes, but observing the Time Activity Curves it can be seen that their trend remains almost constant from 10 minutes onwards. Furthermore, the most significant parameters also used to develop Deep Learning models, are those related to the first 10 minutes of acquisitions [20]. The choice of such acquisition times allowed us to detect the presence of anomalous events and provided an early indication of the need for SUV correction for the PET/CT exam. In our patient cohort, 9 out of 69 abnormal administrations were identified. In particular, 4 cases identified as extravasation were confirmed during PET acquisition.
The attention in this work was focused on the trends analysis of the DR-time curves acquired during the administration of 18F-FDG for PET/CT diagnostic examination (Fig. 1). This monocentric study, despite its statistical limitations, allows identifying the trend of the three different classes of administration (i.e. normal, abnormal, extravasation) similar to those already mentioned in the literature [12, 14, 17, 19].
Although DR-time curves of IV administrations showed similar behaviours in terms of DRinmax, DRinmean, t*, in general three different mean behaviours were noted (Fig. 3), characterised by ΔRt and ΔpinNOR analysis. The boxplots shown in Fig. 4 highlight how the ΔRt value could be able to identify the three different classes of administration. According to the results obtained, if after 10 minutes from the start of injection the ΔRt values are still far from the average value indicated for the normal class (24 ± 11 µSv/h), the patient could present an abnormal case of venous retention, or in the worst case, extravasation. The ΔRt values for the three classes are significantly different (p < 0.05). As shown in Fig. 5, also the normalised ΔpinNOR showed a different behaviour for extravasation cases assuming an average value of 0.44 compared to the average value of (0.91 ± 0.06) and (0.77 ± 0.23) in normal and abnormal classes, respectively.
All the extravasation cases show a percentage variation on SUV that agree with data in the literature, with a maximum percentage variation of 6% [10]. Table 2 presents an inverse proportionality between ΔpinNOR and the percentage variation of ARS and SUV%CR. Instead, it shows a direct proportionality between ΔRt and the percentage variation of ARS and SUV%CR. The ΔpinNOR parameter could intervene in the evaluation of the entity of the phenomenon, returning a priori a percentage directly linked to the ARS. Although the analysis of these two parameters requires further statistical support, the extravasation events' behaviour differs considerably from the two other classes identified.
Figure 6 shows the trend of ΔRtNOR and the inverse of ΔpinNOR in function of SUV correction coefficient. Recalling that ΔpinNOR is a parameter that is calculated on the curve of the injection arm, the fact that both the inverse of ΔpinNOR and ΔRtNOR have the same trend as a function of the SUV correction factor makes us assume that it would suffice to acquire only the time-dependent DR curve of the injection arm to characterise the presence of anomalies or extravasation events in real-time. The possibility of recognizing and monitoring extravasation events using a single sensor placed in the injection site would also allow us to apply this method in cases where injection occurs in areas different from the antecubital fossa (e.g., in the foot) due to difficulties in accessing the blood vessel. Furthermore, the correlation found between the SUV correction factor and the inverse of ΔpinNOR makes us assume that from its calculation, the SUV correction can be estimated before image analysis. This method could greatly speed up SUV correction procedures carried out for diagnostic purposes. These results are presented as a preliminary study whose assumptions may be confirmed by a forthcoming study in which more patients will be involved. Together with the trends analysis of the DR-time curves, we investigated tissue self-dose in the injection area due to extravasation of 18F-FDG. We have identified only three works in the literature that were dedicated to dosimetric extravasation dose estimation due to radiopharmaceuticals [22–24]. We believe that the dosimetric characterization of extravasation events enables clinicians to identify patients at risk of adverse tissue reactions. However, our method has some limitations. First of all, the major source of error in our estimate lies in the choice of using the radiopharmaceutical physical half-time instead of the effective clearance half-time. This choice was made as a precaution, as there was no specific patient curve describing the kinetics of the radiopharmaceutical. In addition, the used dose factors assume to work on a spherical volume and are only an approximation of the segmented anatomical area on the PET images of patients. A voxel-based approach for dose determination with a more refined dose calculation model could be useful to characterise the limits of this approach. Despite these limitations, the dose estimation is consistent with the absence of observable effects, according to the nuclear medicine physician, they aren't serious cases of extravasation given the small percentages of ARS.
The use of the sensors described would make it easier for the healthcare professional in charge of injections to detect extravasations already in the first few minutes after injection. Lightness and great usability encourage further development of this system, which would guarantee a simple method for screening and monitoring IV administration. The real-time detection of DR on the patient’s arms and the reading monitors of devices allows the rapid identification of the ΔRt value, which as described is indicative of identifying abnormal or extravasation cases during injections. In addition, the characterization of the ΔpinNOR parameter may give the opportunity of using only one sensor in the injection zone to characterise extravasation events, as well as allowing the estimation of the SUV correction coefficient.