Imaging of Tumour Microenvironment for the Planning of Oncological Therapies Using Positron Emission Tomography

Tumour cells differ from normal tissue cells in several important ways. These differences, like for example changed energy metabolism, result in altered microenvironment of malignant tumours. Non-invasive imaging of tumour microenvironment has been at the centre of intense research recently due to the important role that this changed environement plays in the development of malignant tumours and due to the role it plays in the treatment of these tumours. In this respect, perhaps the most important characteristics of the tumour microenvironment from this point of view are the lack of oxygen or hypoxia and changes in blood flow (BF). The purpose of this thesis was to investigate the processes of energy metabolism, BF and oxygenation in head and neck cancer and pancreatic tumours and to explore the possibilities of improving the methods for their quantification using positron emission tomography (PET). To this end [18F]EF5, a new PET tracer for detection of tumour hypoxia was investigated. Favourable uptake properties of the tracer were observed. In addition, it was established that the uptake of this tracer does not correlate with the uptake of existing tracers for the imaging of energy metabolism and BF, so the information about the presence of tissue hypoxia cannot therefore be obtained using tracers such as [18F]FDG or [15O]H2O. These results were complemented by the results of the follow-up study in which it was shown that the uptake of [18F]EF5 in head and neck tumours prior to treatment is also associated with the overall survival of the patients, indicating that tumour hypoxia is a negative prognostic factor and might be associated with therapeutic resistance. The influences of energy metabolism and BF on the survival of patients with pancreatic cancer were investigated in the second study. The results indicate that the best predictor of survival of patients with pancreatic cancer is the relationship between energy metabolism and BF. These results suggest that the cells with high metabolic activity in a hypoperfused tissue have the most aggressive phenotype.Siirretty Doriast

Kuvantamistutkimukset endometrioosin diagnostiikassa

Kuvantamistutkimukset ovat keskeinen työväline endometrioosin diagnostiikassa, erityisesti taudin laajuutta kartoitettaessa. Käytetyimmät ja parhaiten soveltuvat menetelmät ovat emättimen kautta tehtävä kaiku- ja magneettitutkimus. Molemmat kuvantamismuodot vaativat perehtyneisyyttä ja ovat yhtä hyviä sairauden toteamisessa. Erityisesti suunniteltaessa leikkaushoitoa endometrioosin laajuus on kartoitettava huolellisesti kuvantamisen avulla

High-intensity focused ultrasound therapy in the uterine fibroid: a clinical case study of poor heating efficacy

A clinical case study of high-intensity focused ultrasound (HIFU) treatment in the uterine fibroid was conducted. During the therapy, poor heating efficacy was observed which could be attributed to several factors such as the local perfusion rate, patient-specific anatomy or changes in acoustic parameters of the ultrasound field. In order to determine the cause of the diminished heating, perfusion analyses and ultrasound simulations were conducted using the magnetic resonance imaging (MRI) data from the treatment. The perfusion analysis showed high local perfusion rate in the myoma (301.0 +- 25.6 mL/100 g/min) compared to the surrounding myometrium (233.8 +- 16.2 mL/100 g/min). The ultrasound simulations did not show large differences in the focal point shape or the acoustic pressure (2.07 +- 0.06 MPa) when tilting the transducer. However, a small shift (-2.2 +- 1.3 mm) in the axial location of the focal point was observed. The main causes for the diminished heating were likely the high local perfusion and ultrasound attenuation due to the deep location of the myoma.Comment: Conference Proceedin

Feasibility of T2 relaxation time in predicting the technical outcome of MR-guided high-intensity focused ultrasound treatment of uterine fibroids

PurposeThe aim of this study was to assess the feasibility of T2 relaxation time in predicting the immediate technical outcome i.e., nonperfused volume ratio (NPVr) of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it with existing T2-weighted imaging methods (Funaki classification and scaled signal intensity, SSI).Materials and methods30 patients with 32 uterine fibroids underwent an MRI study including a quantitative T2 relaxation time measurement prior to MRgHIFU treatment. T2 relaxation times were measured with a multi-echo fast imaging-based technique with 16 echoes. The correlation between pretreatment values of the uterine fibroids and treatment outcomes, that is nonperfused volume ratios (NPVr), was assessed with nonparametric statistical measures. T2 relaxation time-based method was compared to existing T2-weighted imaging-based methods using receiver-operating-characteristics (ROC) curve analysis and Chi-square test.ResultsNonparametric measures of association revealed a statistically significant negative correlation between T2 relaxation time values and NPVr. The T2 relaxation time classification (T2 I, T2 II, and T2 III) resulted in the whole model p-value of 0.0019, whereas the Funaki classification resulted in a p-value of 0.56. The T2 relaxation time classification (T2 I and T2 II) achieved a whole model of a p-value of 0.0024, whereas the SSI classification had a p-value of 0.0749.ConclusionsA longer T2 relaxation time of the fibroid prior to treatment correlated with a lower NPVr. Based on our results, the T2 relaxation time classifications seem to outperform the Funaki classification and the SSI method.</p

Feasibility of apparent diffusion coefficient in predicting the technical outcome of MR-guided high-intensity focused ultrasound treatment of uterine fibroids - a comparison with the Funaki classification

PurposeTo investigate the feasibility of using an apparent diffusion coefficient (ADC) classification in predicting the technical outcome of magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it to the Funaki classification.Materials and methodsForty-two patients with forty-eight uterine fibroids underwent diffusion-weighted imaging (DWI) before MRgHIFU treatment. The DW images were acquired with five different b-values. Correlations between ADC values and treatment parameters were assessed. Optimal ADC cutoff values were determined to predict technical outcomes, that is, nonperfused volume ratios (NPVr) such that three classification groups were created (NPVr of 80%). Results were compared to the Funaki classification using receiver-operating-characteristic (ROC) curve analysis, with statistical significance being tested with the Chi-square test.ResultsA statistically significant negative correlation (Spearman's rho = -0.31, p-value 80%) and 1800 x 10(-6)mm(2)/s (NPVr 80%), ADC II (NPVr 30-80%) and ADC III (NPVr < 30%). Analysis of the whole model area under the curve resulted in values of 0.79 for the ADC classification (p-value = 0.0007) and 0.62 for the Funaki classification (p-value = 0.0527).ConclusionsLower ADC values prior to treatment correlate with higher NPV ratios. The ADC classification seems to be able to predict the NPV ratio and may even outperform the Funaki classification. Based on these results DWI and ADC maps should be included in the MRI screening protocol

Oxytocin selectively reduces blood flow in uterine fibroids without an effect on myometrial blood flow: a dynamic contrast enhanced MRI evaluation

Introduction Uterine fibroids are the most common benign neoplasms in women. The administration of intravenous oxytocin is known to increase the efficacy of a non-invasive thermal ablation method (MR-HIFU) for treating fibroids. However, it is not known whether this phenomenon is caused by the effect of the oxytocin on the myometrium or the fibroid itself. The objective of this study was to evaluate the influence of oxytocin on the blood flow of fibroids, myometrium and skeletal muscle using a quantitative perfusion MRI technique.Materials and methods17 premenopausal women with fibroids considered to be treated with MR-HIFU and 11 women with no fibroids were enrolled in the study. An extended MRI protocol of the pelvis was acquired for each subject. Later another MRI scan was performed with continuous intravenous infusion of oxytocin. The effect of oxytocin was analyzed from quantitative perfusion imaging. The study was registered in clinicaltrials.gov NCT03937401.ResultsOxytocin decreased the blood flow of each fibroid; the median blood flow of fibroid was 39.9 ml/100 g tissue/min without and 3.5 mL/100 g/min with oxytocin (p <= 0.0001). Oxytocin did not affect the blood flow of the myometrium in either group. Oxytocin increased the blood flow of the skeletal muscle in both groups (p = 0.04).ConclusionOxytocin is effective in decreasing the blood flow in fibroids while having minor or no effect on the blood flow of normal myometrium. Routine use of oxytocin in HIFU therapy may make the therapy suitable to a larger group of women in a safe manner

Wedged gel pad for bowel manipulation during MR-guided high-intensity focused ultrasound therapy to treat uterine fibroids: a case report

Magnetic resonance guided high-intensity focused ultrasound (MR-HIFU) therapy is not feasible in all patients with uterine fibroids because of limiting anatomical factors such as scar tissue, bowel loops or other obstacles in the sonication path. These may prevent the treatment or limit the treatment window, and therefore, also the volume where HIFU therapy can be delivered. Bowel loops present a particular problem because of bowel gas bubbles and hard particles which may cause reflection or absorption of ultrasound energy, potentially leading to thermal damage and even bowel perforation. Most commonly used techniques for bowel repositioning are bladder and/or rectum filling but these are not always sufficient to reposition the bowel loops. With more efficient bowel repositioning technique, the number of eligible patients for MR-HIFU treatment could be increased, and therapy efficacy be improved in cases where bowel loops limit the treatment window.A wedged exterior gel pad was used in two patients presented with in total of four symptomatic fibroids undergoing MR-HIFU treatment when bladder and/or rectum filling was not sufficient to reposition the bowel loops. No severe adverse effects were observed in these cases. The non-perfused volume ratios (NPVs) immediately after treatment were 86% and 39% for the first patient, and 3% for the second patient.Our preliminary experience suggests that the use of a wedged gel pad during MR-HIFU treatment could be an effective tool to manipulate the bowels in cases where the bladder and/or rectum filling is not sufficient to reposition the bowel loops. A wedged gel pad could also be used in other situations to achieve better treatment coverage to the uterine fibroid.</p

Munuaiskasvainten kuvantamisohjattujen lämpökoagulaatiohoitojen turvallisuus ja tehokkuus : Turun yliopistollisen sairaalan potilasaineisto vuosilta 2017-2019

JOHDANTO : Munuaiskasvainten kuvantamisohjattu lämpökoagulaatiohoito yleistyy. Etuina leikkaukseen verrattuna ovat vähäisempi kajoavuus, pienempi komplikaatioriski ja lyhyempi sairaalajakso. Tutkimuksemme tavoite oli tutkia komplikaatioiden esiintyvyyttä ja riskitekijöitä, sekä selvittää onkologisia tuloksia. AINEISTO JA MENETELMÄT : Yhteensä 69 potilasta ja 72 munuaiskasvainta hoidettiin kuvantamisohjatulla lämpökoagulaatiohoidolla TYKSissä helmikuusta 2017 lokakuuhun 2019. TULOKSET : Kasvainten keskikoko oli 2,8 cm (1,2-6,6 cm). Komplikaatioita havaittiin neljä (5,8 %). Välittömästi hoidon jälkeen neljässä kasvaimessa havaittiin jäännöskasvaimen epäily ja kuuden kuukauden kuluttua seitsemässä kasvaimessa (9,7 %) todettiin paikallinen uusiminen tai jäännöskasvain. Munuaistoiminnassa ei havaittu muutoksia. PÄÄTELMÄT : Hoito on komplikaatioiden ja munuaistoiminnan säilyttämisen suhteen turvallinen vaihtoehto pienissä kasvaimissa. Hoidon tehokkuus on tyydyttävä, kun huomioidaan sen mini-invasiivisuus sekä uusintahoidon mahdollisuus. Kasvaimen koko ennustaa sekä komplikaatioita että paikallista uusiutumista.</div

Magnetic resonance guided high intensity focused ultrasound for uterine fibroids and adenomyosis has no effect on ovarian reserve

AbstractIntroduction Uterine fibroids are the most common benign tumors in healthy women. High Intensity Focused Ultrasound (HIFU) is a modern, noninvasive thermal ablation method for treating uterine fibroids. There is increasing evidence that ultrasound guided HIFU (US-HIFU) has no adverse impact on ovarian reserve but little data exists on magnetic resonance guided HIFU (MR-HIFU). There are different options to estimate ovarian reserve, perhaps the most reliable being the measurement of serum Anti-Müllerian hormone (AMH).Material and methods Seventy-four (74) premenopausal women with serum AMH 0.1 ug/L or over, aged 24–48 and with fibroids or adenomyosis treated with MR-HIFU were enrolled in our study. AMH levels were analyzed before and 3 months after the MR-HIFU treatment. Correlations between AMH level changes and position of fibroids, fibroid volume, non-perfused volume ratio, and treatment energies were studied.Results The median AMH level before the HIFU treatment was 1.20 (range: 0.1–7.75 ug/L) and after the treatment 1.23 (range: 0.1–8.51 ug/L). No significant change was detected (p = .90). The patients were divided in three subgroups depending on the baseline AMH levels. The changes were not significant in any of the subgroups. Neither did the location of the treated fibroid affect the change of AMH levels nor the total energy used during treatment.Conclusions MR-HIFU does not compromise the ovarian reserve. Neither the location of the treated fibroid nor the total energy used during MR-HIFU had any effect on the change of AMH levels