Medical image computing and computer-aided medical interventions applied to soft tissues. Work in progress in urology

Until recently, Computer-Aided Medical Interventions (CAMI) and Medical Robotics have focused on rigid and non deformable anatomical structures. Nowadays, special attention is paid to soft tissues, raising complex issues due to their mobility and deformation. Mini-invasive digestive surgery was probably one of the first fields where soft tissues were handled through the development of simulators, tracking of anatomical structures and specific assistance robots. However, other clinical domains, for instance urology, are concerned. Indeed, laparoscopic surgery, new tumour destruction techniques (e.g. HIFU, radiofrequency, or cryoablation), increasingly early detection of cancer, and use of interventional and diagnostic imaging modalities, recently opened new challenges to the urologist and scientists involved in CAMI. This resulted in the last five years in a very significant increase of research and developments of computer-aided urology systems. In this paper, we propose a description of the main problems related to computer-aided diagnostic and therapy of soft tissues and give a survey of the different types of assistance offered to the urologist: robotization, image fusion, surgical navigation. Both research projects and operational industrial systems are discussed

New Image Processing Methods for Ultrasound Musculoskeletal Applications

In the past few years, ultrasound (US) imaging modalities have received increasing interest as diagnostic tools for orthopedic applications. The goal for many of these novel ultrasonic methods is to be able to create three-dimensional (3D) bone visualization non-invasively, safely and with high accuracy and spatial resolution. Availability of accurate bone segmentation and 3D reconstruction methods would help correctly interpreting complex bone morphology as well as facilitate quantitative analysis. However, in vivo ultrasound images of bones may have poor quality due to uncontrollable motion, high ultrasonic attenuation and the presence of imaging artifacts, which can affect the quality of the bone segmentation and reconstruction results. In this study, we investigate the use of novel ultrasonic processing methods that can significantly improve bone visualization, segmentation and 3D reconstruction in ultrasound volumetric data acquired in applications in vivo. Specifically, in this study, we investigate the use of new elastography-based, Doppler-based and statistical shape model-based methods that can be applied to ultrasound bone imaging applications with the overall major goal of obtaining fast yet accurate 3D bone reconstructions. This study is composed to three projects, which all have the potential to significantly contribute to this major goal. The first project deals with the fast and accurate implementation of correlation-based elastography and poroelastography techniques for real-time assessment of the mechanical properties of musculoskeletal tissues. The rationale behind this project is that, iii in the future, elastography-based features can be used to reduce false positives in ultrasonic bone segmentation methods based on the differences between the mechanical properties of soft tissues and the mechanical properties of hard tissues. In this study, a hybrid computation model is designed, implemented and tested to achieve real time performance without compromise in elastographic image quality . In the second project, a Power Doppler-based signal enhancement method is designed and tested with the intent of increasing the contrast between soft tissue and bone while suppressing the contrast between soft tissue and connective tissue, which is often a cause of false positives in ultrasonic bone segmentation problems. Both in-vitro and in-vivo experiments are performed to statistically analyze the performance of this method. In the third project, a statistical shape model based bone surface segmentation method is proposed and investigated. This method uses statistical models to determine if a curve detected in a segmented ultrasound image belongs to a bone surface or not. Both in-vitro and in-vivo experiments are performed to statistically analyze the performance of this method. I conclude this Dissertation with a discussion on possible future work in the field of ultrasound bone imaging and assessment

The impact of functional imaging on radiation medicine

Radiation medicine has previously utilized planning methods based primarily on anatomic and volumetric imaging technologies such as CT (Computerized Tomography), ultrasound, and MRI (Magnetic Resonance Imaging). In recent years, it has become apparent that a new dimension of non-invasive imaging studies may hold great promise for expanding the utility and effectiveness of the treatment planning process. Functional imaging such as PET (Positron Emission Tomography) studies and other nuclear medicine based assays are beginning to occupy a larger place in the oncology imaging world. Unlike the previously mentioned anatomic imaging methodologies, functional imaging allows differentiation between metabolically dead and dying cells and those which are actively metabolizing. The ability of functional imaging to reproducibly select viable and active cell populations in a non-invasive manner is now undergoing validation for many types of tumor cells. Many histologic subtypes appear amenable to this approach, with impressive sensitivity and selectivity reported

MR imaging of osteochondral grafts and autologous chondrocyte implantation

Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible

Registration and Segmentation of Multimodality Images for Post Processing of Skeleton in Preclinical Oncology Studies

Advancements in medical imaging techniques provide biomedical researchers with quality anatomical and functional information inside preclinical subjects in the fields of cancer, osteopathic, cardiovascular, and neurodegenerative research. The throughput of the preclinical imaging studies is a critical factor which determines the pace of small animal medical research. The time involved in manual analysis of large amount of imaging data prior to data interpretation by the researcher, limits the number of studies in a time frame. In the proposed solution, an automated image segmentation method was used to segment individual vertebrae in mice. Individual vertebrae of MOBY atlas were manually segmented and registered to the CT data. The PET activity for L1-L5 vertebrae was measured by applying the CT registered atlas vertebrae ROI. The algorithm was tested on three datasets from a PET/CT bone metastasis study using 18F-NaF radiotracer. The algorithm was found to reduce the analysis time threefold with a potential to further reduce the automated analysis time by use of computer system with better specification to run the algorithm. The manual analysis value can vary each time the analysis is performed and is dependent on the individual performing the analysis. Also the error percent was recorded and showed an increasing trend as the analysis moves down the spine from skull to caudal vertebrae. This method can be applied to segment the rest of the bone in the CT data and act as the starting point for the registration of the soft tissues

Magneettikuvauksella ohjattu korkean intensiteetin kohdennettu ultraääniteknologia syöpätautien liitännäishoidoissa ja syöpälääkkeiden annostelussa

Ablative hyperthermia (more than 55 °C) has been used as a stand-alone treatment for accessible solid tumors not amenable to surgery, whereas mild hyperthermia (40-45 °C) has been shown effective as an adjuvant for both radiotherapy and chemotherapy. An optimal mild hyperthermia treatment is noninvasive and spatially accurate, with precise and homogeneous heating limited to the target region. High-intensity focused ultrasound (HIFU) can noninvasively heat solid tumors deep within the human body. Magnetic resonance imaging (MRI) is ideal for HIFU treatment planning and monitoring in real time due to its superior soft-tissue contrast, high spatial imaging resolution, and the ability to measure temperature changes. The combination of MRI and HIFU therapy is known as magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU). Low temperature-sensitive liposomes (LTSLs) release their drug cargo in response to heat (more than 40 °C) and may improve drug delivery to solid tumors when combined with mild hyperthermia. MR-HIFU provides a way to image and control content release from imageable low-temperature sensitive liposomes (iLTSLs). This ability may enable spatiotemporal control over drug delivery - a concept known as drug dose painting. The objectives of this dissertation work were to develop and implement a clinically relevant volumetric mild hyperthermia heating algorithm, to implement and characterize different sonication approaches (multiple foci vs. single focus), and to evaluate the ability to monitor and control heating in real time using MR-HIFU. In addition, the ability of MR-HIFU to induce the release of a clinical-grade cancer drug encapsulated in LTSLs was investigated, and the potential of MR-HIFU mediated mild hyperthermia for clinical translation as an image-guided drug delivery method was explored. Finally, drug and contrast agent release of iLTSLs as well as the ability of MR-HIFU to induce and monitor the content release were examined, and a computational model that simulates MR-HIFU tissue heating and drug delivery was validated. The combination of a multifoci sonication approach and the mild hyperthermia heating algorithm resulted in precise and homogeneous heating limited to the targeted region both in vitro and in vivo. Heating was more spatially confined compared to the use of single focus sonication method. The improvement in spatial control suggests that multifoci heating is a useful tool in MR-HIFU mediated mild hyperthermia applications for clinical oncology. Using the mild hyperthermia heating algorithm, LTSL + MR-HIFU resulted in significantly higher tumor drug concentrations compared to free drug and LTSL alone. This technique has potential for clinical translation as an image-guided drug delivery method. MR-HIFU also enabled real-time monitoring and control of iLTSL content release. Finally, computational models may allow quantitative in silico comparison of different MR-HIFU heating algorithms as well as facilitate therapy planning for this drug delivery technique.Ablatiivista hypertermiaa (yli 55 °C) on perinteisesti käytetty leikkauksiin soveltumattomien kasvainten hoitoon. Lievän hypertermian (40-45 °C) on sen sijaan todettu olevan tehokas liitännäishoito syöpätautien säde- ja lääkehoidoille. Suotuisa hypertermiahoito on kajoamatonta ja täsmällisesti kohdistettua. Lämmityksen tulisi lisäksi olla tarkkaa, tasalaatuista ja kohdealueeseen rajoittunutta. Korkean intensiteetin kohdennettu ultraääni (HIFU) -hoito mahdollistaa kasvainten kajoamattoman lämmityksen. Magneettikuvauksen (MK) etuina ovat erinomainen pehmytkudoskontrasti, korkea paikkaresoluutio ja kyky mitata lämpötilan muutoksia. Näin ollen MK soveltuu erinomaisesti HIFU -hoitojen suunnitteluun ja seurantaan. MK:n ja HIFU:n yhdistelmää kutsutaan magneettikuvauksella ohjatuksi korkean intensiteetin kohdennetuksi ultraääniteknologiaksi (MR-HIFU). Lämpötilaherkät liposomit ovat suunniteltuja vapauttamaan lääkeainesisältönsä hieman normaalia ruumiinlämpötilaa korkeammissa lämpötiloissa (yli 40 °C). Yhdessä lievän hypertermian kanssa tämänkaltaiset liposomit voivat mahdollistaa kohdistetun lääkeaineen vapauttamisen. Liposomien sisällön vapautumisen tarkkailu voi myös mahdollistaa tarkan lääkemäärän kohdistetun annostelun kasvaimessa. Väitöskirjatyössä kehitettiin kliinisesti merkittävä lämmitysalgoritmi lievän hypertermian aikaansaamiseksi, toteutettiin usean samanaikaisen kohteen sonikaatio (ultraäänialtistus) menetelmä sekä arvioitiin algoritmin ja menetelmän kykyä kontrolloida kudoksen lämpötilaa käyttäen kliinistä MR-HIFU laitetta. Lisäksi tutkittiin HIFU:n kykyä vapauttaa lääkeaine lämpötilaherkistä liposomeista, karakterisoitiin lääke- ja kontrastiaineen vapautuminen kuvannettavissa olevista lämpötilaherkistä liposomeista sekä tarkasteltiin MR-HIFU:lla aikaansaadun lievän hypertermian potentiaalia kohdentaa lääkeaineen vapautuminen kasvaimeen. Tässä työssä myös validoitiin laskennallinen malli, joka simuloi MR-HIFU:lla aikaansaatua lämmitystä ja siitä johtuvaa lääkeaineen vapautumista, sekä todennettiin MR-HIFU:n sopivuus lämpöablaatioon perustuvaan kohdun pehmytkudoskasvainten hoitomenelmään kliinisessä käytössä. Lievän hypertermian lämmitysalgoritmi yhdessä usean kohteen sonikaatiomenetelmän kanssa tuotti täsmällisen, tasalaatuisen sekä paikallisesti rajoitetun lämmityksen kohdealueessa. Usean kohteen sonikaatiomenetelmä voi siis olla hyödyllinen työkalu MR-HIFU:n lievän hypertermian syöpähoidon sovelluksissa. MR-HIFU yhdessä lämpötilaherkkien liposomien kanssa sai aikaan merkittävästi korkeamman kasvaimen lääkeainekonsentraation verrokkiryhmiin nähden, ja saattaa siten soveltua kliiniseen käyttöön kuvantamisavusteisena lääkehoitona. Liposomien sisällön (lääkeaine + MK-kontrastiaine) vapautumisen kuvannettavuus merkitsee, että MR-HIFU saattaa lisäksi mahdollistaa tarkan lääkeannoksen kohdistetun vapauttamisen

Quantification of bone using a 3.0 tesla clinical magnetic resonance scanner

The work in this thesis examines the potential of using magnetic resonance imaging and spectroscopy (MRI & MRS) as a quantitative tool for diagnosing bone abnormalities at multiple skeletal sites, which could be used in conjunction with routine clinical imaging.MRI and MRS are routinely used in the clinical setting for the diagnosis of various types of diseases and abnormalities due to its advantages of providing excellent soft tissue contrast and also providing physiological and metabolic information. The use of MRI and MRS as a direct diagnostic tool for bone abnormalities is very limited at the moment due to issues of costs and standardisation. The aim in this thesis was to use the clinical 3.0 T MR scanner to acquire data from bone and bone marrow for identification of structural and chemical properties and to use those features to identify differences in bone strength and condition. The volunteers in this thesis were part of the high bone mass (HBM) study and they had additional acquisitions from dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT).MR acquisition protocols have been successfully optimised for each type of bone region and in-house software has also been created to process the acquired data and quantify various types of structural and chemical properties.The MR data from distal radius and tibia demonstrated good correlation with pQCT data (e.g. Figure 8-2 & Figure 8-3) and were also able to differentiate between HBM-affected and control populations (e.g. Figure 8-26). The MR data from lumbar vertebrae also demonstrated good correlation with DEXA data and some of the measurements were also able to differentiate between the HBM-affected and control populations.The combined results from this thesis demonstrate that both MRI and MRS are sensitive techniques for measurement of bone quantity and quality, and they are ready to be applied for clinical investigation as part of routine clinical imaging to identify bone strength in relation to abnormalities and treatments

Ultrasound imaging of cervical spine motion for extreme acceleration environments

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2011.Cataloged from PDF version of thesis. Vita.Includes bibliographical references (p. 52-55).Neck and back pain is one of the most common musculoskeletal complaints in personnel in variable acceleration environments such as astronauts and military pilots. Ultrasound is known for dynamic imaging and diagnostic workup of the axial and appendicular skeleton, but is not currently used to image the cervical spine, the injury of which may change the biomechanics of the cervical vertebrae, which CT and MRI (the current gold standard in cervical spine imaging) are poor at capturing. To validate ultrasound as a modality for imaging dynamic motion of the cervical spine several experiments were performed in static and dynamic human and animal (ovine) models: 1. Static analysis of ex-vivo ovine cervical spines imaged by ultrasound, MRI, and CT demonstrated that the imaging modality affected the measured intervertebral disc height (p<0.01); similar evaluation was done in-vivo in Emergency Department patients who received a CT scan as part of their clinical course that showed that ultrasound could fit into existing clinical workflows. 2. Dynamic analysis of isolated ex-vivo ovine cervical spinal segments intervertebral disc displacement with a mounted ultrasound probe demonstrated a measurement uncertainty of ± 0.2 mm and no bias at low frequency sinusoidal spinal displacement. A similar evaluation in-vivo with humans with an ultrasound probe mounted on a cervical-collar found a 0.8-1.3 mm amount of cervical spine distraction from the C4-5 Functional Spinal Unit. In human cadavers subjected to passive flexion and extension of the cervical spine, ultrasound measurements of the relative flexion/extension angles between consecutive cervical vertebrae were similar to fluoroscopy. 3. Ultrasound was able to record dynamic motion of the cervical spine in-vivo in running on a treadmill, during parabolic flight, and traveling over a rough road in a military vehicle. The ultrasound methods developed and tested in this thesis could provide an inexpensive, portable and safe technique that can identify and characterize cervical spine anatomy and pathology.Funding Acknowledgment: National Space Biomedical Research Institute, Army Research Office, Children's Hospital Orthopedic Surgery Foundationby Daniel Miller Buckland.Ph.D