Update on the ICUD-SIU consultation on multi-parametric magnetic resonance imaging in localised prostate cancer

Introduction: Prostate cancer (PCa) imaging is a rapidly evolving field. Dramatic improvements in prostate MRI during the last decade will probably change the accuracy of diagnosis. This chapter reviews recent current evidence about MRI diagnostic performance and impact on PCa management. Materials and methods: The International Consultation on Urological Diseases nominated a committee to review the literature on prostate MRI. A search of the PubMed database was conducted to identify articles focussed on MP-MRI detection and staging protocols, reporting and scoring systems, the role of MP-MRI in diagnosing PCa prior to biopsy, in active surveillance, in focal therapy and in detecting local recurrence after treatment. Results: Differences in opinion were reported in the use of the strength of magnets [1.5 Tesla (T) vs. 3T] and coils. More agreement was found regarding the choice of pulse sequences; diffusion-weighted MRI (DW-MRI), dynamic contrast-enhanced MRI (DCE MRI), and/or MR spectroscopy imaging (MRSI) are recommended in addition to conventional T2-weighted anatomical sequences. In 2015, the Prostate Imaging Reporting and Data System (PI-RADS version 2) was described to standardize image acquisition and interpretation. MP-MRI improves detection of clinically significant PCa (csPCa) in the repeat biopsy setting or before the confirmatory biopsy in patients considering active surveillance. It is useful to guide focal treatment and to detect local recurrences after treatment. Its role in biopsy-naive patients or during the course of active surveillance remains debated. Conclusion: MP-MRI is increasingly used to improve detection of csPCa and for the selection of a suitable therapeutic approach

Theoretical investigation of transgastric and intraductal approaches for ultrasound-based thermal therapy of the pancreas.

BackgroundThe goal of this study was to theoretically investigate the feasibility of intraductal and transgastric approaches to ultrasound-based thermal therapy of pancreatic tumors, and to evaluate possible treatment strategies.MethodsThis study considered ultrasound applicators with 1.2 mm outer diameter tubular transducers, which are inserted into the tissue to be treated by an endoscopic approach, either via insertion through the gastric wall (transgastric) or within the pancreatic duct lumen (intraductal). 8 patient-specific, 3D, transient, biothermal and acoustic finite element models were generated to model hyperthermia (n = 2) and ablation (n = 6), using sectored (210°-270°, n = 4) and 360° (n = 4) transducers for treatment of 3.3-17.0 cm3 tumors in the head (n = 5), body (n = 2), and tail (n = 1) of the pancreas. A parametric study was performed to determine appropriate treatment parameters as a function of tissue attenuation, blood perfusion rates, and distance to sensitive anatomy.ResultsParametric studies indicated that pancreatic tumors up to 2.5 or 2.7 cm diameter can be ablated within 10 min with the transgastric and intraductal approaches, respectively. Patient-specific simulations demonstrated that 67.1-83.3% of the volumes of four sample 3.3-11.4 cm3 tumors could be ablated within 3-10 min using transgastric or intraductal approaches. 55.3-60.0% of the volume of a large 17.0 cm3 tumor could be ablated using multiple applicator positions within 20-30 min with either transgastric or intraductal approaches. 89.9-94.7% of the volume of two 4.4-11.4 cm3 tumors could be treated with intraductal hyperthermia. Sectored applicators are effective in directing acoustic output away from and preserving sensitive structures. When acoustic energy is directed towards sensitive structures, applicators should be placed at least 13.9-14.8 mm from major vessels like the aorta, 9.4-12.0 mm from other vessels, depending on the vessel size and flow rate, and 14 mm from the duodenum.ConclusionsThis study demonstrated the feasibility of generating shaped or conformal ablative or hyperthermic temperature distributions within pancreatic tumors using transgastric or intraductal ultrasound

Determination of Thermal Dose Model Parameters Using Magnetic Resonance Imaging

Magnetic Resonance Temperature Imaging (MRTI) is a powerful technique for noninvasively monitoring temperature during minimally invasive thermal therapy procedures. When coupled with thermal dose models, MRTI feedback provides the clinician with a real-time estimate of tissue damage by functioning as a surrogate for post-treatment verification imaging. This aids in maximizing the safety and efficacy of treatment by facilitating adaptive control of the damaged volume during therapy. The underlying thermal dose parameters are derived from laboratory experiments that do not necessarily reflect the surrogate imaging endpoints used for treatment verification. Thus, there is interest and opportunity in deriving model parameters from clinical procedures that are tailored to radiologic endpoints. The objective of this work is to develop and investigate the feasibility of a methodology for extracting thermal dose model parameters from MR data acquired during ablation procedures. To this end, two approaches are investigated. One is to optimize model parameters using post-treatment imaging outcomes. Another is to use a multi-parametric pulse sequence designed for simultaneous monitoring of temperature and damage dependent MR parameters. These methodologies were developed and investigated in phantom and feasibility established using retrospective analysis of in vivo thermal therapy treatments. This technique represents an opportunity to exploit experimental data to obtain thermal dose parameters that are highly specific for clinically relevant endpoints

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

TULSA (transurethral ultrasound ablation) on kokeellinen magneettikuvantamisohjattu hoitomuoto eturauhassairauksien hoitoon. Sen vaikutus perustuu virtsaputken kautta lähetettäviin ultraääniaaltoihin, jotka kuumentavat eturauhaskudosta. Eturauhaskudoksen lämpötilan nousu yli 55 asteen aiheuttaa välittömän koagulaationekroosiin, johon menetelmän terapeuttinen vaikutus perustuu. Hoidon aikana seurataan reealiaikaisesti kohdekudoksen lämpötilamuutoksia lämpöherkillä magneettikuvilla, MRI-termometrialla, jonka avulla voidaan varmistaa haluttu lämpövaikutus eturauhasessa. Nopea ja korkea lämpötilan nousu saattaa kuitenkin aiheuttaa termofiksaatioksi kutsutun ilmiön, jossa kudos vaikuttaa morfologisesti elinkelpoiselta, vaikka todellisuudessa kudos saattaa olla tuhoutunut. Tämän tutkimuksen tarkoitus oli määrittää epäilyjen termofiksoituneiden eturauhasalueiden elinkelpoisuus ja kuvailla näiden immunoprofiilia. Prospektiivisissa tutkimuksessa (ClinicalTrials.gov: NCT03350529) 6 potilaan eturauhassyövät hoidettiin TULSA-hoidolla. Jokaisella potilaalla oli magneettikuvantamisella todennettu ja biopsiavarmennettu eturauhassyöpä ja jokaiselle potilaalle tehtiin gadolinium-tehosteinen magneettikuvaus ja eturauhasen poistoleikkaus kolme viikkoa TULSA-hoidon jälkeen. Leikkauksessa poistetuille eturauhasille tehtiin normaali histopatologinen tutkimus. Mikäli epävarmuus täydellisestä nekroosista hematosykliini-eosiinivärjäyksen jälkeen jäi, tehtiin immunohistokemiallinen värjäys. Ablaatioalueen vertailukohtana morfologian tutkimisessa käytettiin eturauhasen lämpövaikutukselta välttynyttä kudosta. Yhdellä potilaalla todettiin termofiksaatio. Alue sijaitsi ablaatioalueen sisällä kohdassa, jossa MRI-termometriassa lämpötila oli ollut korkeimmillaan. Alueen verisuonitus oli myös täysin hävinnyt gadolinium-tehosteisissa magneettikuvissa. Ympärillä oleva kudos oli hematosykliini-eosiinivärjäyksessä nekrotisoitunut. Elinkelpoiselta näyttäneen kudoksen immunoprofiilissa paljastui termofiksaatioon sopivia värjäysmallin muutoksia. Tärkeimpänä todisteena termofiksaatiosta oli Cam5.2- vasta-aineella havaittu cytokeratin 8 -värjäyksen negatiivisuus. Laaja kirjallisuuskatsaus tukee näitä havaintoja eturauhasesta ja muista kudoksista havaituista termofiksaatioista. Termofiksoituneet solut siis voivat säilyttää morfologiansa hematosykliini-eosiinvärjäyksessä. Mikäli termofiksoituneita alueita ei tunnisteta tai ei tutkita immunohistokemiallisesti, voi lopputuloksena olla väärä päättely hoidon epäonnistumisesta. Aikasempaan kirjallisuuteen ja tähän tutkimukseen perustuen Cam5.2. värjäys cytokeratin 8:lle vaikuttaa olevan käytännöllinen ja luotettava apuväline termofiksoituneiden solujen erottamiseksi elinkelpoisista soluista

New Technology and Techniques for Needle-Based Magnetic Resonance Image-Guided Prostate Focal Therapy

The most common diagnosis of prostate cancer is that of localized disease, and unfortunately the optimal type of treatment for these men is not yet certain. Magnetic resonance image (MRI)-guided focal laser ablation (FLA) therapy is a promising potential treatment option for select men with localized prostate cancer, and may result in fewer side effects than whole-gland therapies, while still achieving oncologic control. The objective of this thesis was to develop methods of accurately guiding needles to the prostate within the bore of a clinical MRI scanner for MRI-guided FLA therapy. To achieve this goal, a mechatronic needle guidance system was developed. The system enables precise targeting of prostate tumours through angulated trajectories and insertion of needles with the patient in the bore of a clinical MRI scanner. After confirming sufficient accuracy in phantoms, and good MRI-compatibility, the system was used to guide needles for MRI-guided FLA therapy in eight patients. Results from this case series demonstrated an improvement in needle guidance time and ease of needle delivery compared to conventional approaches. Methods of more reliable treatment planning were sought, leading to the development of a systematic treatment planning method, and Monte Carlo simulations of needle placement uncertainty. The result was an estimate of the maximum size of focal target that can be confidently ablated using the mechatronic needle guidance system, leading to better guidelines for patient eligibility. These results also quantified the benefit that could be gained with improved techniques for needle guidance

Novel imaging and image-guided therapy of prostate cancer

Whole-gland prostate surgery and radiotherapy, the established approaches to localised prostate cancer (PCa), usually cause substantial adverse effects. Targeted image-guided cancer therapy has gained acceptance through improved PCa detection, localization and characterization by magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET-CT). Focal therapy offers a potentially better trade-off between disease control and preservation of genitourinary and bowel function. MRI-guided transurethral ultrasound ablation (TULSA), a recently introduced treatment modality, uses therapeutic ultrasound directed through the urethra to thermally ablate the prostate under real-time MRI control. The applicability of TULSA to focal therapy of primary PCa, palliative therapy of symptomatic locally advanced PCa, and treatment of locally radiorecurrent PCa was investigated in a prospective setting. TULSA was shown to be a safe and effective method for local PCa control. Thermal injury was restricted to the planned treatment volume. This method enabled whole-gland ablation and focal ablation anywhere in the prostate. Furthermore, TULSA achieved local symptom relief in palliative care and encouraging preliminary oncological control in salvage care. These promising phase 1 study results enabled progression to phase 2 studies of patients with localised PCa and salvage of patients with radiorecurrent PCa. The diagnostic accuracy of MRI and PSMA PET-CT was studied to determine the extent of primary PCa, to plan TULSA treatment and evaluate treatment response. PSMA PET-CT was found to be a more sensitive method for detecting metastatic disease and appeared to accurately reflect the extent of local disease before and after TULSA treatment. PSMA PET-CT appears to detect some falsepositive bone lesions. The advantages of using MRI and PSMA PET-CT in treatment planning and monitoring treatment response are under further investigation. These studies have shown 18F-PSMA-1007 PET-CT to be effective in PCadiagnosis and TULSA to be effective in PCa therapyModernit kuvantamismenetelmät ja kuvantamisohjatut hoidot eturauhassyövässä Vakiintuneet paikallisen eturauhassyövän (PCa) hoitomenetelmät, leikkaus ja sädehoito, kohdistuvat koko rauhaseen ja aiheuttavat merkittäviä haittavaikutuksia. Magneettikuvantamisella (MRI) ja eturauhassyövän entsyymikuvantamisella (PSMA PET-TT) PCa:n havaitseminen, paikallistaminen ja karakterisointi ovat tarkentuneet. Kohdennetut kuvantamisohjatut syöpähoidot ovat siksi saaneet hyväksynnän ja tarjoavat mahdollisesti optimaalisemman vaihtoehdon hoidon hyödyn ja sen virtsa- ja sukupuolielimiin kohdistuvien haittojen suhdetta ajatellen. MRI-ohjattu eturauhasen kuumennushoito (TULSA) on uusi menetelmä, jossa virtsaputken kautta kudosta tuhoavaa ultraääntä ohjataan eturauhaseen reaaliaikaisessa MRI-ohjauksessa ja -valvonnassa. TULSA:n käyttökelpoisuutta primaarin PCa:n kohdennetussa hoidossa, paikallisesti edenneen PCa:n palliatiivisessa hoidossa ja sädehoidon jälkeen paikallisesti uusiutuneen PCa:n hoidossa tutkittiin prospektiivisessa tutkimusasetelmassa. TULSA-menetelmän todettiin tuhoavan turvallisesti ja tehokkaasti eturauhaskudosta. Lämpövaurio rajautui suunnitellulle hoitoalueelle. Menetelmä mahdollisti kuumennushoidon käytön kaikkialla eturauhasessa, koko rauhasessa tai paikallisemmin. Lisäksi TULSA-hoito lievensi paikallisoireita palliatiivisilla potilailla ja oli tehokas sädehoidon jälkeen paikallisesti uusiutuneessa PCa:ssä. Lupaavien ensimmäisen vaiheen tutkimustulosten takia olemme siirtyneet toisen vaiheen tutkimuksiin näillä uusilla indikaatioilla. MRI:n ja PSMA PET-TT:n diagnostista tarkuutta tutkittiin primaarin PCa:n levinneisyyden selvittelyssä ja TULSA-hoidon suunnittelussa sekä hoitovasteen arvioinnissa. PSMA PET-TT:n havaittiin olevan herkempi menetelmä etäpesäkkeiden tunnistamisessa ja se näytti tarkasti taudin laajuuden ennen ja jälkeen TULSAhoidon. PSMA PET-TT tunnistaa myös vääriä positiivisia luustomuutoksia. MRI:n ja PSMA PET-TT:n kliinistä hyötyä TULSA-hoidon suunnittelussa ja hoitovasteen seurannassa tutkitaan edelleen. Tutkimuksemme ovat osoittaneet PSMA PET-TT:n hyödyllisyyden PCa:n diagnostiikassa ja TULSA:n turvallisuuden ja tehon PCa:n hoidossa

Magnetic resonance imaging for localization of prostate cancer in the setting of biochemical recurrence

The clinical suspicion of local recurrence of prostate cancer after radical treatment is based on the onset of biochemical failure. The use of multiparametric magnetic resonance imaging (MRI) for prostate cancer has increased over recent years, mainly for detection, staging, and active surveillance. However, suspicion of recurrence in the set of biochemical failure is becoming a significant reason for clinicians to request multiparametric MRI. Radiologists should be able to recognize the normal posttreatment MRI findings. Fibrosis and atrophic remnant seminal vesicles (SV) after radical prostatectomy are often found and must be differentiated from local relapse. Moreover, brachytherapy, external beam radiotherapy, and focal therapies tend to diffusely decrease the signal intensity of the peripheral zone on T2-weighted images due to the loss of water content, consequently mimicking tumor and hemorrhage. The combination of T2-weighted images and functional studies like diffusion-weighted imaging and dynamic contrast-enhanced imaging improves the identification of local relapse. Tumor recurrence tends to restrict on diffusion images and avidly enhances after contrast administration. The authors provide a review of the normal findings and the signs of local tumor relapse after radical prostatectomy, external beam radiotherapy, brachytherapy and focal therapies

Stochastic Data Assimilation Approaches for Magnetic Resonance Temperature Imaging

During magnetic resonance (MR)-guided thermal therapies, proton resonance frequency shift (PRFS) based MR temperature imaging can quantitatively monitor tissue temperature changes. It is widely known that the PRFS technique is easily perturbed by tissue motion, tissue susceptibility changes, magnetic field drift, and modality–dependent applicator induced artifacts. Due to recent advances in computational algorithms and hardware, much more powerful statistical analysis methods are becoming realizable in the real-time processing environment. To this end, my dissertation research focused on the development, validation, and implementation of stochastic data-driven processing techniques to increase the robustness of MR temperature monitoring during thermal therapies. MR temperature imaging was demonstrated to achieve a high degree of accuracy in damage predictions during rapid ablation procedures. In the event of temperature imaging data loss, a Kalman filtered MR temperature imaging algorithm using an uncorrelated, sparse covariance matrix for a Pennes bioheat model was developed to predict temperature in regions of missing or erroneous measurement. Temperature predictions were demonstrated to be accurate, while being less computationally expensive than the dense covariance matrix used in standard Kalman filtering. A second approach developed and investigated was the use of a Gaussian process for MR temperature imaging to allow for an accurate probabilistic extrapolation of the background phase. The technique demonstrated reliable temperature estimates in the presence of unwanted background field changes. The Gaussian process algorithm was also implemented to forecast temperature using a limited number of a priori temperature images. The performance of these proposed approaches was validated in simulations, ex vivo, and in vivo. These techniques allow for a full probabilistic prediction and an estimate of the uncertainty that provide a statistical model for MR temperature imaging. In conclusion, I have developed two novel approaches to MR temperature imaging post-processing and demonstrated the feasibility of application of these stochastic, data-driven models developed to improve the robustness of MR-guidance during thermal therapies and potentially enhance the safety and efficacy of treatment

Focused ultrasound for treatment of bone tumours.

PURPOSE: Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions. METHODS: A comprehensive literature search and review of abstracts presented at the recently completed fourth International Focused Ultrasound Symposium was performed. Case reports and older publications revisited in more recent studies were excluded. For clinical studies that extend beyond bone tumours, only the data regarding bone tumours are presented. RESULTS: Fifteen studies assessing the use of focused ultrasound in treatment of primary benign bone tumours, primary malignant tumours, and metastatic tumours meeting the search criteria were identified. For these clinical studies the responders group varied within 91-100%, 85-87% and 64-94%, respectively. Major complications were reported in the ranges 0%, 0-28% and 0-4% for primary benign, malignant and metastatic tumours, respectively. CONCLUSIONS: Image-guided FUS is both safe and effective in the treatment of primary and secondary tumours. Additional phase III trials are warranted to more fully define the role of FUS in treatment of both benign and malignant bone tumours

Image-guided focal therapy for prostate cancer

The adoption of routine prostate specific antigen screening has led to the discovery of many small and low-grade prostate cancers which have a low probability of causing mortality. These cancers, however, are often treated with radical therapies resulting in long-term side effects. There has been increasing interest in minimally invasive focal therapies to treat these tumors. While imaging modalities have improved rapidly over the past decade, similar advances in image-guided therapy are now starting to emerge—potentially achieving equivalent oncologic efficacy while avoiding the side effects of conventional radical surgery. The purpose of this article is to review the existing literature regarding the basis of various focal therapy techniques such as cryotherapy, microwave, laser, and high intensity focused ul­trasound, and to discuss the results of recent clinical trials that demonstrate early outcomes in patients with prostate cancer