Détection du cancer de la peau par tomographie d'impédance électrique

RÉSUMÉ Au cours des trente dernières années, l’augmentation du taux d’incidence du cancer de la peau a été la plus importante parmi tous les cancers. Le diagnostic précoce du cancer de la peau s’avère important pour minimiser les risques d’évolution en cancer généralisé. Ce diagnostic implique habituellement une inspection visuelle suivie d’une biopsie si la lésion est jugée suspecte par le clinicien. Des études récentes indiquent que le quart des lésions cancéreuses ne sont pas détectées à un stade précoce diminuant ainsi le pronostic du patient. De plus, plusieurs lésions biopsiées s’avèrent non cancéreuses, augmentant ainsi les risques d’infection tout en causant un stress inutile au patient dans l’attente des résultats histopathologiques. Pour détecter précocement le cancer de la peau, une nouvelle technique biomédicale s’avère prometteuse : la tomographie d’impédance électrique (TIE). La TIE est une technique d’imagerie médicale qui permet de visualiser la distribution de conductivité électrique d’une section du corps. Celle-ci se base sur le principe que les propriétés électriques de chaque tissu biologique varient de façon spécifique en fonction de la fréquence. Les images sont reconstruites à partir d’une série de mesures acquises à l’aide d’électrodes placées autour de la région d’intérêt. Ces mesures sont effectuées en utilisant toutes les combinaisons possibles de quatre électrodes : deux pour appliquer un courant de faible amplitude et deux autres pour mesurer la tension résultante. Comme les propriétés électriques des lésions cancéreuses et non cancéreuses diffèrent en fonction de la fréquence, les images de conductivité obtenues par TIE permettraient de les discriminer objectivement. L’objectif général de ce projet de doctorat consiste à développer un système de TIE permettant de détecter le cancer de la peau. Les objectifs spécifiques sont : 1) développer un modèle par éléments finis de la peau, 2) développer les algorithmes de reconstruction d’images, 3) adapter un système de TIE au contexte dermatologique et 4) valider le système en effectuant des tests expérimentaux. ----------ABSTRACT Over the past thirty years, skin cancer incidence rate has increased the most significantly among all cancers. Early stage skin cancer diagnosis is essential to minimize risks of developing metastases. Diagnosis usually involves visual inspection followed by histopathological examination if the lesion is suspected malignant by the clinician. Recent studies however suggest that a quarter of lesions remain undetected at an early stage which adversely affects the patient’s prognosis. Furthermore, many excised lesions are found not cancerous increasing risks of infection and causing unnecessary stress to the patient awaiting histopathological results. For early stage skin cancer diagnosis, a new biomedical technique seems promising: electrical impedance tomography (EIT). EIT is a medical imaging technique used to visualize the electric conductivity distribution of a body segment. EIT is based on the principle that electrical properties of every biological tissue specifically vary as a function of frequency. Images are reconstructed from a set of measurements acquired with electrodes applied around the region of interest. Measurements are performed using all possible combinations of four electrodes: two are used to apply a low amplitude current while two others are used to measure the resulting voltage. Since malignant and benign lesions have different cellular characteristics, their impedance signature as a function of frequency differs and they can therefore be objectively discriminated by EIT. The main objective of this PhD project is to develop an EIT system for skin cancer screening. The specific objectives are: 1) to develop a finite element model of the skin, 2) to develop image reconstruction algorithms, 3) to adapt an EIT system to the dermatology context, and 4) to validate the system experimentally. Since no EIT system has been developed for skin cancer screening, a finite element model of the skin was first developed to study the electrical behavior of the skin, identify optimal frequencies to discriminate lesions, and solve the forward problem of EIT

Non-invasive hemodynamic monitoring by electrical impedance tomography

The monitoring of central hemodynamic parameters such as cardiac output (CO) and pulmonary artery pressure (PAP) is of paramount clinical importance to assess the health status of the cardiovascular system. However, their measurement requires the insertion of a pulmonary artery catheter, a highly invasive procedure associated with non-negligible morbidity and mortality rates. In this thesis, we investigated the clinical potential of electrical impedance tomography (EIT) - a radiation-free medical imaging technique - as a non-invasive alternative for the measurement of CO and PAP. In a first phase, we investigated the potential of EIT for the measurement of CO. This measurement is implicitly based on the hypothesis that the EIT heart signal (the ventricular component of the EIT signals) is induced by ventricular blood volume changes. This hypothesis has never been formally investigated, and the exact origins of the EIT heart signal remain subject to interpretation. Therefore, using a model, we investigated the genesis of this signal by identifying its various sources and their respective contributions. The results revealed that the EIT heart signal is dominated by cardioballistic effects (heart motion). However, although of prominently cardioballistic origin, the amplitude of the signal has shown to be strongly correlated to stroke volume (r = 0.996, p < 0.001; error of 0.57 +/- 2.19 mL). We explained these observations by the quasi-incompressibility of myocardial tissue and blood. We further identified several factors and conditions susceptible to affect the accuracy of the measurement. Finally, we investigated the influence of the EIT sensor belt position on the measured heart signal. We observed that small belt displacements - likely to occur in clinical settings during patient handling - can induce errors of up to 30 mL on stroke volume estimation. In a second phase, we investigated the feasibility of a novel method for the non-invasive measurement of PAP by EIT. The method is based on the physiological relation linking the PAP to the velocity of propagation of the pressure waves in the pulmonary arteries. We hypothesized that the variations of this velocity, and therefore of the PAP, could be measured by EIT. In a bioimpedance model of the human thorax, we demonstrated the feasibility of our method in various types of pulmonary hypertensive disorders. Our EIT-derived parameter has shown to be particularly well-suited for predicting early changes in pulmonary hemodynamics due to its physiological link with arterial compliance. Finally, we validated experimentally our method in 14 subjects undergoing hypoxia-induced PAP changes. Significant correlation coefficients (range: [0.70, 0.98], average: 0.89) and small standard errors of the estimate (range: [0.9, 6.3] mmHg, average: 2.4 mmHg) were found between our EIT-derived systolic PAP and reference systolic PAP values obtained by Doppler echocardiography. In conclusion, there is a promising outlook for EIT in non-invasive hemodynamic monitoring. Our observations provide novel insights for the interpretation and understanding of EIT heart signals, and detail the physiological and metrological requirements for an accurate measurement of CO by EIT. Our novel PAP monitoring method, validated in vivo, allows a reliable tracking of PAP changes, thereby paving the way towards the development of a new branch of non-invasive hemodynamic monitors based on the use of EIT

Noninvasive Stroke Volume Monitoring by Electrical Impedance Tomography

In clinical practice it is of vital importance to track the health of a patient's cardiovascular system via the continuous measurement of hemodynamic parameters. Cardiac output (CO) and the related stroke volume (SV) are two such parameters of central interest as they are closely linked with oxygen delivery and the health of the heart. Many techniques exist to measure CO and SV, ranging from highly invasive to noninvasive ones. However, none of the noninvasive approaches are reliable enough in clinical settings. To overcome this limitation, we investigated the feasibility and practical applicability of noninvasively measuring SV via electrical impedance tomography (EIT), a safe and low-cost medical imaging modality. In a first step, the unclear origins of cardiosynchronous EIT signals were investigated in silico on a 4D bioimpedance model of the human thorax. Our simulations revealed that the EIT heart signal is dominated by ventricular activity, giving hope for a heart amplitude-based SV estimation. We further showed via simulations that this approach seems feasible in controlled scenarios but also suffers from some limitations. That is, EIT-based SV estimation is impaired by electrode belt displacements and by changes in lung conductivity (e.g. by respiration or liquid redistribution). We concluded that the absolute measurement of SV by EIT is challenging, but trending - that is following relative changes - of SV is more promising. In a second step, we investigated the practical applicability of this approach in three experimental studies. First, EIT was applied on 16 mechanically ventilated patients in the intensive care unit (ICU) receiving a fluid challenge to improve their hemodynamic situation. We showed that the resulting relative changes in SV could be tracked using the EIT lung amplitude, while this was not possible via the heart amplitude. The second study, performed on patients in the operating room (OR), had to be prematurely terminated due to too low variations in SV and technical challenges of EIT in the OR. Finally, the third experimental study aimed at testing an improved measurement setup that we designed after having identified potential limitations of available clinical EIT systems. This setup was tested in an experimental protocol on 10 healthy volunteers undergoing bicycle exercises. Despite the use of subject-specific 3D EIT, neither the heart nor the lung amplitudes could be used to assess SV via EIT. Changes in electrode contact and posture seem to be the main factors impairing the assessment of SV. In summary, based on in silico and in vivo investigations, we revealed various challenges related to EIT-based SV estimation. While our simulations showed that trending of SV via the EIT heart amplitude should be possible, this could not be confirmed in any of the experimental studies. However, in the ICU, where sufficiently controlled EIT measurements were possible, the EIT lung amplitude showed potential to trend changes in SV. We concluded that EIT amplitude-based SV estimation can easily be impaired by various factors such as electrode contact or small changes in posture. Therefore, this approach might be limited to controlled environments with the least possible changes in ventilation and posture. Future research should scrutinize the lung amplitude-based approach in dedicated simulations and clinical trials