Phd in MORPHOGENESIS AND TISSUE ENGINEERING

Thesis title: Body K-Tomography

The biological issue addressed The potassium (K) monitoring is crucial to diagnose the serious manifestations of hypokalemia and hyperkalaemia, which can involve several diseases, often life-threatening, such as muscle weakness or paralysis, cardiac conduction abnormalities or arrhythmias. Covid-19 has recently been found to cause hypokalemia, too. Unfortunately, the currently available methods for K monitoring are based on in vitro measurements, and so a real-time monitoring is not allowed. Herein the first non-invasive wearable detector, which measures in vivo potassium, is proposed. It uses the intrinsic radioactivity of one K isotope, the 40K, in equilibrium with stable isotopes 39K and 41K. Therefore neither invasive nor additional radiation are needed, only the one already present in human body. Moreover, it performs a direct in-vivo measurement on intracellular K, ensuring a higher accuracy and allowing a continuous monitoring of patient potassium, remotely too. Results The proposed detector is composed by five NaI scintillators (diameter 2.5cm, length 10cm) optionally coupled to 5 Silicon Photo Multiplier arrays. A feasibility study of such detector, placed close to human liver, was carried out. First, the radiation background was estimated, both with theoretical evaluation (520 gamma/s) and with experimental measurements (220 gamma/s). Then, detection and geometrical efficiency were assessed. The geometrical efficiency estimation was obtained with the computational human phantoms (also known as voxel phantoms), from CTs of real patients. In the CT images of these patients, the segmentation of organs with not negligible potassium amount was carried out. With a statistical method, based on the isotropic generation of 1k gamma events and on the count of photons impinging on the detector, it was possible to assess geometrical efficiency. The detector position relative to patient was finally selected, in order to maximize geometrical efficiency. The overall efficiency resulted 0.2%. The comparison of the amount of K used for detection, between the proposed method and the standard method based on the blood sampling, was reported. In the first case the detector gets information from 8.3g of K, mainly present in the liver and in muscles, which lead to a concentration of 0.54 mg of K per Kg, taking into account the detector efficiency. In the latter case, the information comes from the sample (5ml) of serum, where the K concentration is 120 mg/l. Assuming a 100% efficiency, the K used in this electrochemical measurement is 0.6mg. Since the project goal is the early hypokalemia diagnosis, as required for the quick treatment of the covid patient, the detector has been tested for the detection of pathological potassium reduction (for moderate hypokalemia the reduction is above 25%). To test the discrimination between the measurements with and without K reduction, the parametric Z test was used. The minimum detectable activity as a function of measuring time, pathological potassium reduction and confidence level has finally been obtained. Conclusions Herein a proposal of the first non invasive wearable in vivo intracelullar potassium measuring detector is reported. It has been designed overcoming many experimental challenges, first of all low counts 40K activity, thanks to a trade off for several problems as cheapness, weight and signal (human 40K radioactive emissions) to noise (background radiation) ratio. It will be particularly useful for territorial health structures, because they will be able to monitor the bedridden patient from their home. Costly and unnecessary mass hospitalizations will therefore be avoided.