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

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

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

Guest Editorial : Special issue on advanced computing for image-guided intervention

Editorial Guest Editorial: Special issue on advanced computing for image-guided intervention In the past years, we have witnessed a growing number of applications of minimally invasive or non-invasive interventions in clinical practice, where imaging is playing an essential role for the success of both diagnosis and therapy. Particularly, advanced signal and image processing algorithms are receiving increasing attention, which aim to provide accurate and reliable information directly to physicians. We have seen the applications of these technologies during all stages of an intervention, including preoperational planning, intra-operational guidance and post-operational verification. For this special issue, we have received a significant number of submissions from both academia and industry, out of which we have carefully selected eleven articles with outstanding quality. These articles have covered the topics of anatomic structure identification and tracking, image registration, data visualization and newly emerging applications. In [1] have addressed the image registration problem between preand post-radiated MRI to facilitate the evaluation of the therapeutic response after External Beam Radiation Treatment (EBRT) for the prostate cancer. A different approach has been employed by We have also included three papers on ultrasound-guided image interventions. In We have included in this special issue two papers on tissue characterization from endoscopic images. Nawarathna et al. have proposed in With the increasing use of various imaging modalities in image-guided intervention and therapy, how to optimally present and visualize the data becomes also an important issue. In [10], the authors have addressed the use of autostereoscopic volumetric visualization of the patient's anatomy, which has the potential to be combined with augmented reality. The paper especially addresses the latency problem in the visualization chain, and a few improvements have been proposed. A new adjacent application has been presented in In summary, we have seen from submissions to this special issue a growing interest in applying advanced signal and image processing technologies to image-guided interventions. The submissions have covered a wide range of clinical applications using various imaging modalities. Image feature extraction remains to be an important subject and it has to be specifically designed to suit the needs for specific applications. Learning-based approaches have also attracted a lot of attention, especially in applications requiring automatic tissue characterization and classification. We are also very happy to have received new emerging applications which are able to extend the traditional interventional imaging into greater application areas. Acknowledgments We would like to thank all the reviewers who have helped to peer-review the submitted papers and their constructive comments are well appreciated

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

Comparison between A-mode and B-mode ultrasound in local hyperthermia monitoring

Hyperthermia therapy is one of the therapy methods used for cancer treatment. It has shown to be an effective way of treating the cancerous tissue when compared to surgery, chemotherapy and radiation. However, real time monitoring method is capable in delivering a consistent heat and preventing any damages to the nearby tissue. Ultrasound is among the widely used technique in clinical setting. A-Mode ultrasound involves one-dimensional (1D) signal processing which enables a quantitative measurement on different types of breast tissues to be conducted faster as it has relatively simple signal processing requirement. On the other hand, B-Mode ultrasound offers good spatial resolution for thermal monitoring. Therefore, the aim of this study is to investigate and to compare the most optimum A-Mode and B-Mode ultrasound parameters to monitor hyperthermia in normal and pathological breast tissue. A series of experiment was conducted on 40 female Sprague Dawley rats. The pathological and normal rats were dissected and exposed to hyperthermia at variation temperature of 37oC (body temperature) and 40oC, 45oC, 50oC and 55oC for hyperthermia temperatures. A-Mode and B-Mode of 7.5 Mhz and 6Mhz was used simultaneously during the experiment for collecting acoustic information and scanning purposes before and after the hyperthermia exposure. Result obtained shows that, for normal tissue condition of both A-Mode and B-Mode, the attenuation calculation to mean of pixel intensity found to be (3.59±0.04)dB and 187.68 at temperature value of 50 oC. Meanwhile, in pathological tissue condition, the attenuation value with respect to pixel intensity was obtained by (3.36±0.26)dB at temperature value of 45oC and 199.26 was achieved at temperature value of 40oC. For backscatter coefficient to variance analysis, the result found that, in both A-Mode and B-Mode normal tissue condition, at temperature value of 40oC, (1.81±0.25) of backscatter coefficient was obtained while at 45oC, the variance value of 3298.94 was achieved. In pathological tissue, the temperature value of 40oC and 55oC was the most pronounce temperature dependent of (1.45±0.28) for backscatter coefficient with respect to 3275.35 of variance analysis. The result obtained from artificial neural network have shown that, 91.67% to 87.5% of testing to validation percentage accuracy of A-Mode was achieved, while in B-Mode, 88.89% and 81.25% of testing and validation data was obtained. Therefore, it is shown that, the use of A-Mode with comparison to B-Mode ultrasound can be used as another potential approach since its attenuation to pixel intensity and backscatter coefficient with respect to variance of A-Mode and B-Mode is very sensitive to the tissue structure in monitoring hyperthermia therapy with respect to the changes of temperature

Molecular Imaging

The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world

Collagen 1 fibers and hypoxic tumor microenvironments in breast cancer and their effect on transport of molecules within the tumor matrix

The work presented in this thesis represents a culmination of four years of research work focused on understanding the role of collagen I (Col1) fibers, a major component of the tumor extracellular matrix in breast cancer. We have investigated the relationship of Col1 fibers with metastasis, hypoxia, macromolecular transport, water diffusion and fractional anisotropy using clinical breast cancer specimens and human breast cancer xenografts genetically engineered to fluoresce under hypoxia. The thesis describes in the detail of the rationale, study design, results and discussion for our studies, which have been either published or submitted as four separate papers. The work here also presents multimodal in vivo imaging techniques which could be used clinically for non-invasive diagnoses of breast cancer progression. These techniques will help provide better patient management