3-D Motion-Tracking for High-Intensity Focused Ultrasound Therapy

Respiratory motion during high-intensity focused ultrasound (HIFU) therapy reduces the efficiency of the treatment in abdominal organs. Hence, for the purpose of motion-correction during HIFU therapy, two different ultrasound-based 3-D motion-tracking methods were presented and adapted to the existing Philips Sonalleve MR-HIFU platform. The displacement estimation accuracies of these two techniques were determined using a metal pin and an in vitro tissue sample as targets. The measurement data was collected on all movement directions using element clusters consisting of one, three and 32 transmitting transducer elements. Simulations of the acoustic fields were also performed in order to discuss the theoretical limitations of the motion-tracking with the existing HIFU system. The displacement estimation accuracies did not differ significantly for the two different techniques introduced but was rather dependent on the transmitting element cluster size and the orientation of the ultrasound beam axis. Using smaller number of elements and defining the beam axis angle accurately in the calculation algorithm yielded more stable results. The motion-tracking using the in vitro tissue sample was significantly more difficult to achieve than with the metal pin target. This was due to the incorrect time-shift values given by the cross-correlation algorithm. Hence, the failed channels had to be manually excluded from the calculations in order to yield the correct displacement estimation values. The introduced motion-tracking methods cannot be readily used as such during clinical HIFU therapy treatment, because the incorrect time-shift values had to be manually excluded from the calculation algorithm. This process could probably be automated by observing the peak count and the amplitude of the cross-correlation curves. However, this method was not verified in this thesis and hence requires further research about its feasibility.Korkeaintensiteettisen fokusoidun ultraääniterapian (HIFU) aikana tapahtuva hengitys vähentää hoidon lämmitystehoa vatsa-alueen elimissä, mikä voidaan kompensoida reaaliaikaisella 3-D -liikkeenkorjauksella. Siksi tässä työssä esitettiin kaksi eri liikkeenseurantamenetelmää, jotka voidaan integroida sellaisenaan Philips Sonalleve MR-HIFU -terapia-alustaan. Näiden menetelmien tarkkuudet mitattiin käyttämällä seurattavina kohteina metallista neulaa sekä kudosnäytettä, joiden avulla mittausdata kerättiin kaikilta liikesuunnilta hyödyntäen yhtä, kolmea ja 32:ta lähettävää ultraäänielementtiä. Lisäksi näiden elementtijoukkojen akustiset kentät simuloitiin, jotta voitiin selvittää esiteltyjen liikkeenseurantamenetelmien teoreettiset rajoitukset käytetyllä HIFU-alustalla. Liikkeenseurantatarkkuudet eivät eronneet merkittävästi kahden esitetyn menetelmän välillä, vaan tarkkuus oli ennemminkin riippuvainen käytetyn elementtijoukon koosta sekä ultraäänikeilan suunnasta. Pienemmän elementtijoukon käyttäminen ja ultraäänikeilan asennon oikea määrittäminen paransivat saatujen mittaustulosten toistettavuutta. Liikkeenseuranta käyttäen kohteena kudosnäytettä oli huomattavasti vaikeampaa kuin metallineulan seuraaminen, mikä johtui ristikorrelaatioalgoritmin antamista vääristä aika-arvoista. Tämän takia ne piti manuaalisesti poistaa laskennasta oikean tuloksen saamiseksi. Esitettyjä liikkeenseurantamenetelmiä ei voida sellaisenaan hyödyntää kliinisessä HIFU-terapiassa, koska väärät aika-arvot piti manuaalisesti poistaa laskenta-algoritmista. Tämä prosessi olisi mahdollisesti voitu automatisoida seuraamalla ristikorrelaatiokäyrien huippumääriä ja amplitudeja. Kyseistä menetelmää ei kuitenkaan verifioitu tässä työssä, minkä takia vaadittaisiin lisätutkimuksia sen toteuttamiskelpoisuudesta

Full modelling of high-intensity focused ultrasound and thermal heating in the kidney using realistic patient models

Objective: High-intensity focused ultrasound (HIFU) therapy can be used for non-invasive treatment of kidney (renal) cancer, but the clinical outcomes have been variable. In this study, the efficacy of renal HIFU therapy was studied using nonlinear acoustic and thermal simulations in three patients. Methods: The acoustic simulations were conducted with and without refraction in order to investigate its effect on the shape, size and pressure distribution at the focus. The values for the attenuation, sound speed, perfusion and thermal conductivity of the kidney were varied over the reported ranges to determine the effect of variability on heating. Furthermore, the phase aberration was studied in order to quantify the underlying phase shifts using a second order polynomial function. Results: The ultrasound field intensity was found to drop on average 11.1 dB with refraction and 6.4 dB without refraction. Reflection at tissue interfaces was found to result in a loss less than 0.1 dB. Focal point splitting due to refraction significantly reduced the heating efficacy. Perfusion did not have a large effect on heating during short sonication durations. Small changes in temperature were seen with varying attenuation and thermal conductivity, but no visible changes were present with sound speed variations. The aberration study revealed an underlying trend in the spatial distribution of the phase shifts. Conclusion: The results show that the efficacy of HIFU therapy in the kidney could be improved with aberration correction. Significance: A method is proposed by which patient specific pre-treatment calculations could be used to overcome the aberration and therefore make ultrasound treatment possible.Comment: Journal paper, IEEE Transactions on Biomedical Engineering (2018

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

The effect of tissue physiological variability on transurethral ultrasound therapy of the prostate

Therapeutic ultrasound is an investigational modality which could potentially be used for minimally invasive treatment of prostate cancer. Computational simulations were used to study the effect of natural physiological variations in tissue parameters on the efficacy of therapeutic ultrasound treatment in the prostate. The simulations were conducted on a clinical ultrasound therapy system using patient computed tomography (CT) data. The values of attenuation, perfusion, specific heat capacity and thermal conductivity were changed within their biological ranges to determine their effect on peak temperature and thermal dose volume. Increased attenuation was found to have the biggest effect on peak temperature with a 6.9% rise. The smallest effect was seen with perfusion with +-0.2% variation in peak temperature. Thermal dose was mostly affected by specific heat capacity which showed a 20.7% increase in volume with reduced heat capacity. Thermal conductivity had the smallest effect on thermal dose with up to 2.1% increase in the volume with reduced thermal conductivity. These results can be used to estimate the interpatient variation during the therapeutic ultrasound treatment of the prostate.Comment: Conference proceedin

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

Salvage Magnetic Resonance Imaging–guided Transurethral Ultrasound Ablation for Localized Radiorecurrent Prostate Cancer: 12-Month Functional and Oncological Results

BackgroundUp to half of all men who undergo primary radiotherapy for localized prostate cancer (PCa) experience local recurrence.ObjectiveTo evaluate the safety and early functional and oncological outcomes of salvage magnetic resonance imaging–guided transurethral ultrasound ablation (sTULSA) for men with localized radiorecurrent PCa.Design, setting, and participantsThis prospective, single-center phase 1 study (NCT03350529) enrolled men with biopsy-proven localized PCa recurrence after radiotherapy. Multiparametric magnetic resonance imaging (mpMRI) and 18F prostate-specific membrane antigen-1007 (18F PSMA-1007) positron emission tomography (PET)-computed tomography (CT) were used to confirm organ-confined disease localization. Patients underwent either whole-gland or partial sTULSA, depending on their individual tumor characteristics.Outcome measurements and statistical analysisPatients were followed at 3-mo intervals. Adverse events (AEs, Clavien-Dindo scale), functional status questionnaires (Expanded Prostate Cancer Index [EPIC]-26, International Prostate Symptom Score, International Index of Erectile Function-5), uroflowmetry, and prostate-specific antigen (PSA) were assessed at every visit. Disease control was assessed at 1 yr using mpMRI and 18F-PSMA-1007 PET-CT, followed by prostate biopsies.Results and limitationsEleven patients (median age 69 yr, interquartile range [IQR] 68–74) underwent sTULSA (3 whole-gland, 8 partial sTULSA) and have completed 12-mo follow-up. Median PSA was 7.6 ng/ml (IQR 4.9–10) and the median time from initial PCa diagnosis to sTULSA was 11 yr (IQR 9.5–13). One grade 3 and three grade 2 AEs were reported, related to urinary retention and infection. Patients reported a modest degradation in functional status, most significantly a 20% decline in the EPIC-26 irritative/obstructive domain at 12 mo. A decline in maximum flow rate (24%) was also observed. At 1 yr, 10/11 patients were free of any PCa in the targeted ablation zone, with two out-of-field recurrences. Limitations include the nonrandomized design, limited sample size, and short-term oncological outcomes.ConclusionssTULSA appears to be safe and feasible for ablation of radiorecurrent PCa, offering encouraging preliminary oncological control.Patient summaryWe present safety and 1-yr functional and oncological outcomes of magnetic resonance imaging–guided transurethral ultrasound ablation (TULSA) as a salvage treatment for local prostate cancer recurrence after primary radiation. Salvage TULSA is safe and shows the ability to effectively ablate prostate cancer recurrence, with acceptable toxicity.</div

Histopathological evaluation of prostate specimens after thermal ablation may be confounded by the presence of thermally-fixed cells

Purpose: Prostate cancer can be eradicated with heat exposure. However, high and rapid temperature elevations may cause thermofixation giving the appearance of viable tissue. The purpose was to characterize the immunoprofile and evaluate the viability of prostate regions with suspected thermofixation. Methods and materials: A prospective, ethics-approved and registered study (NCT03350529) enrolled six patients with MRI-visible, biopsy-concordant prostate cancer to undergo lesion-targeted MRI-guided transurethral ultrasound ablation (TULSA) followed by radical prostatectomy at 3 weeks, to evaluate the accuracy and efficacy of TULSA with whole-mount histology as a reference standard. If ambiguity about complete necrosis within the ablated region remained after hematoxylin-eosin staining, viability was assessed by immunohistochemistry. Treatment day MRI-thermometry and 3-week contrast-enhanced MRI post-TULSA were examined to assess ablation success and correlation with histopathology. Results: One patient presented with an apparently viable subregion inside the ablated area, surrounded by necrosis on H&E staining, located where temperature was highest on MRI-thermometry and tissues completely devascularized on MRI. Immunoprofile of the apparently viable tissue revealed changes in staining patterns suggesting thermofixation; the most significant evidence was the negative cytokeratin 8 staining detected with Cam5.2 antibody. A comprehensive literature review supports these observations of thermofixation with similar findings in prostate and other tissues. Conclusion: Thermally-fixed cells can sustain morphology on H&E staining. Misinterpretation of treatment failure may occur, if this phenomenon is not recognized and immunohistochemistry performed. Based on the previous literature and the current study, Cam5.2 staining for cytokeratin 8 appears to be a practical and reliable tool for distinguishing thermally-fixed from viable cells.</p