Haptic assessment of tissue stiffness in locating and identifying gynaecological cancer in human tissue

Gynaecological surgeons are not able to gather adequate tissue feedback during minimal access surgery for cancer treatment. This can result in failure to locate tumour boundaries and to ensure these are completely resected within tumour-free resection margins. Surgeons achieve significantly better surgical and oncological outcomes if they can identify the precise location of a gynaecological tumour. Indeed, the true nature of tumour, whether benign or cancerous, is often not known prior to surgery. If more details were available in relation to the characteristics that differentiate gynaecological cancer in tumours, this would enable more accurate diagnosis and help in the planning of surgery. HYPOTHESIS: Haptic technology has the potential to enhance the surgeon’s degree of perception during minimal access surgery. Alteration in tissue stiffness in gynaecological tumours, thought to be associated with the accelerated multiplication of cancer cells, should allow their location to be identified and help in determining the likelihood of malignancy. METHOD: Setting: (i) Guy's & St Thomas' Hospital (ii) Dept of Informatics (King's College London).Permission from the National Research Ethics Committee and Research & Development (R&D) approval were sought from the National Health Service. The Phantom Omni, capable of 3D motion tracking, attached to a nano-17 force sensor, was used to capture real-time position data and force data. Uniaxial indentation palpation behaviour was used. The indentation depth was calculated using the displacement of the probe from the surface to the deepest point for each contact. The tissue stiffness (TS) was then calculated.The haptic probe was tested first on silicone models with embedded nodules mimicking tumour(s). This was followed by assessing TS ex-vivo using a haptic probe on fresh human gynaecological organs that had been removed in surgery. Tissue stiffness maps were generated in real time using the haptic device by converting stiffness values into RGB values. Surgeons also manually palpated and recorded the site of the tumour. Histology was used as the gold standard for location and cancer diagnosis. Manual palpation and haptic data were compared for accuracy on tumour location. The tissue stiffness calculated by the haptic probe was compared in cancer and control specimens. Several data analysis techniques were applied to derive results.CONTRIBUTIONS: Haptic indentation probe was tested for the first time on fresh human gynaecological organs to locate cancer in a clinical setting. We are the first one to evaluate the accuracy of cancer diagnosis in human gynaecological organs with a force sensing haptic indentation probe measuring tissue stiffness

Development of a Harmonic Motion Imaging guided Focused Ultrasound system for breast tumor characterization and treatment monitoring

Breast cancer is the most common cancer and the second leading cause of cancer death among women. About 1 in 8 U.S. women (about 12%) will develop invasive breast cancer over the course of their lifetime. Existing methods of early detection of breast cancer include mammography and palpation, either by patient self-examination or clinical breast exam. Palpation is the manual detection of differences in tissue stiffness between breast tumors and normal breast tissue. The success of palpation relies on the fact that the stiffness of breast tumors is often an order of magnitude greater than that of normal breast tissue, i.e., breast lesions feel ''hard'' or ''lumpy'' as compared to normal breast tissue. A mammogram is an x-ray that allows a qualified specialist to examine the breast tissue for any suspicious areas. Mammography is less likely to reveal breast tumors in women younger than 50 years with denser breast than in older women. When a suspicious site is detected in the breast through a breast self-exam or on a screening mammogram, the doctor may request an ultrasound of the breast tissue. A breast ultrasound can provide evidence about whether the lump is a solid mass, a cyst filled with fluid, or a combination of the two. An invasive needle biopsy is the only diagnostic procedure that can definitely determine if the suspicious area is cancerous. In the clinic, 80% of women who have a breast biopsy do not have breast cancer. Most women with breast cancer diagnosed will have some type of surgery to remove the tumor. Depending on the type of breast cancer and how advanced it is, the patient might need other types of treatment as well, such as chemotherapy and radiation therapy. Image-guided minimally-invasive treatment of localized breast tumor as an alternative to traditional breast surgery, such as high intensity focused ultrasound (HIFU) treatment, has become a subject of intensive research. HIFU applies extreme high temperatures to induce irreversible cell injury, tumor apoptosis and coagulative necrosis. Compared with conventional surgical procedures the main advantages of HIFU ablation lie in the fact that it is non-invasive, less scarring and less painful, allowing for shorter recovery time. HIFU can be guided by MRI (MRgFUS) or by conventional diagnostic ultrasound (USgFUS). Worldwide, thousands of patients with uterine fibroids, liver cancer, breast cancer, pancreatic cancer, bone tumors, and renal cancer have been treated by USgFUS. In this dissertation, the objective is to develop an integrated Harmonic Motion Imaging guided Focused Ultrasound (HMIgFUS) system as a clinical monitoring technique for breast HIFU with the added capability of detecting tumors for treatment planning, evaluation of tissue stiffness changes during HIFU ablation for treatment monitoring in real time, and assessment of thermal lesion sizes after treatment evaluation. A new HIFU treatment planning method was described that used oscillatory radiation force induced displacement amplitude variations to detect the HIFU focal spot before lesioning. Using this method, we were able to visualize the HMIgFUS focal region at variable depths. By comparing the estimated displacement profiles with lesion locations in pathology, we demonstrated the feasibility of using this HMI-based technique to localize the HIFU focal spot and predict lesion location during the planning phase. For HIFU monitoring, a HIFU lesion detection and ablation monitoring method was first developed using oscillatory radiation force induced displacement amplitude variations in real time. Using this method, the HMIgFUS focal region and lesion formation were visualized in real time at a feedback rate of 2.4 Hz. By comparing the estimated lesion size against gross pathology, the feasibility of using HMIgFUS to monitor treatment and lesion formation without interruption is demonstrated. In order to reduce the imaging time, it is shown in this dissertation that using the steered FUS beam, HMI can be used to image a 2.3 times larger ROI without requiring physical movement of the transducer. Using steering for HMI can be used to shorten the total imaging duration without requiring physical movement of the transducer. For the application of breast tumor, HMI and HMIgFUS were optimized and applied to ex vivo breast tissue. The results showed that HMI is experimentally capable of mapping and differentiating stiffness in normal and abnormal breast tissues. HMIgFUS can also successfully generate thermal lesions on normal and pathological breast tissues. HMI has also been applied to post-surgical breast mastectomy specimens to mimic the in vivo environment. In the end, the first HMI clinical system has been built with added capability of GUP-based parallel beamforming. A clinical trial has been approved at Columbia University to image breast tumor on patient. The HMI clinical system has shown to be able to map fibroadenoma mass on two patients with valid HMI displacement. The study in this dissertation may yield an early-detection technique for breast cancer without any age discrimination and thus, increase the survival rate

Entwicklung und Anwendung der in vivo abdominellen Magnetresonanzelastographie

Magnetic Resonance Elastography (MRE) is a well-established non-invasive imaging technique used to quantify the mechanical properties of tissues in vivo for the diagnosis of liver fibrosis. However, MRE is limited by its spatial resolution, sensitivity to motion artifacts, and insensitivity to metabolic function. Therefore, three studies of abdominal MRE were conducted to improve the quality of mechanical maps for characterizing liver tumors, to correct for motion artifacts induced by breathing, and to implement MRE on a PET/MRI scanner to correlate mechanical liver properties with metabolic functions in small animals through technical improvements in image acquisition and post-processing. High-resolution stiffness (shear wave speed in m/s), wave penetration (penetration rate in m/s), and fluidity (phase of the complex shear modulus in rad) maps were generated using multifrequency MRE, novel actuators, and tomoelastography post-processing. The first study characterized the stiffness and fluidity of a total of 141 liver tumors in 70 patients. The second study analyzed the motion of abdominal organs and its effect on their stiffness using different acquisition paradigms and image registration in 12 subjects. The third study examined the relationship of liver stiffness and wave penetration to central metabolic liver functions in 19 rabbits. Malignant liver tumors were distinguished from the surrounding liver (stiffness area under the curve [AUC]: 0.88 and fluidity AUC: 0.95) and benign tumors (stiffness AUC: 0.85 and fluidity AUC: 0.86) due to their increased stiffness and fluidity. In the second study, no significant differences in stiffness were observed despite significant differences in examination time, organ motion, and image quality with different image acquisition paradigms. Motion correction by image registration increased image sharpness, so that no significant difference was measurable between MRE in free breathing and breath-hold. Healthy rabbit livers showed heterogeneous liver stiffness, such that division into low and high stiffness (>1.6 m/s) groups resulted in significant differences in central metabolic functions. Stiffness and fluidity measured by multifrequency MRE hold promise as quantitative biomarkers for the diagnosis of malignant liver tumors. Abdominal MRE with free breathing, followed by image registration, is recommended as the best balance between fast examination time and good image quality. Additionally, the applicability of abdominal MRE in small animals in a clinical MRI was demonstrated, and correlations between mechanical liver properties and metabolic functions were found. This study demonstrates improvements in the quality of maps of biophysical parameters for both clinical and preclinical studies, making an important contribution to the clinical translation of multifrequency MRE as a non-invasive imaging modality for abdominal organs and pathologies.Die Magnetresonanzelastographie (MRE) ist eine nichtinvasive Bildgebungsmethode zur Quantifizierung mechanischer Gewebeeigenschaften in vivo bei der Diagnose von Leberfibrose. Limitationen bestehen aufgrund örtlicher Bildauflösung, Bewegungsempfindlichkeit und Insensitivität zu metabolischen Funktionen. Aufgrund technischer Verbesserung in der Bildaufnahme und der Bildauswertung wurde daher anhand von drei Studien zur abdominellen MRE die Bildqualität mechanischer Karten zur Charakterisierung von Lebertumoren verbessert, atmungsinduzierte Organbewegungen korrigiert und die MRE an klinischen PET/MRT implementiert, um an Kleintieren die mechanischen Lebereigenschaften mit metabolischen Funktionen zu korrelieren. Mittels multifrequenter MRE, neuartiger Aktoren und tomoelastographischer Auswertung wurden hochaufgelöste Karten der Steifigkeit (Scherwellengeschwindigkeit in m/s), Wellenpenetration (Wellenpenetrationsrate in m/s) und Fluidität (Phase des komplexen Schermoduls in rad) generiert. Die erste Studie charakterisierte die Steifigkeit und Fluidität von insgesamt 141 Lebertumoren an 70 Patienten. Eine zweite Studie analysierte die Bewegung und den Einfluss auf die Steifigkeit abdomineller Organe mittels unterschiedlicher Aufnahmeparadigmen und Bildregistrierung in 12 Probanden. In einer dritten Studie wurde der Zusammenhang von Lebersteifigkeit und Wellenpenetration zu zentralen metabolischen Leberfunktionen an 19 Kaninchen untersucht. Maligne Lebertumoren können durch erhöhte Steifigkeit und Fluidität (Steifigkeit AUC: 0.88 und Fluidität AUC: 0.95) gut von gutartigen Tumoren (Steifigkeit AUC: 0.85 und Fluidität AUC: 0.86) unterschieden werden. In der zweiten Studie wurden trotz verschiedener Aufnahmeparadigmen und Unterschiede in Untersuchungsdauer, Organbewegung und Bildqualität keine signifikanten Unterschiede in der Organsteifigkeit festgestellt. Die Bildregistrierung verbesserte die Bildschärfe, sodass kein signifikanter Unterschied zwischen freier Atmung und Atempause messbar war. Kaninchenlebern zeigten heterogene Steifigkeiten, sodass eine Zweiteilung in niedrige und hohe Steifigkeit (>1.6 m/s) signifikante Unterschiede in zentralen metabolischen Funktionen zeigte. Steifigkeit und Fluidität, die mittels der Mehrfrequenz-MRE gemessen werden, stellen vielversprechende quantitative Biomarker für die Diagnose maligner Lebertumoren dar. Abdominelle MRE in freier Atmung mit Bildregistrierung ist der beste Kompromiss aus schneller Untersuchungsdauer und guter Bildqualität. Die Anwendbarkeit an Kleintieren in einem klinischen MRT wurde gezeigt, inklusive Korrelationen zwischen mechanischen Lebereigenschaften und metabolischen Funktionen. Diese Arbeit konnte somit die Bildqualität mechanischer Karten sowohl für klinische als auch präklinische Untersuchungen verbessern und damit einen wichtigen Beitrag zur Translation der Multifrequenz-MRE als klinisch angewandte nichtinvasive Bildgebungsmethode abdomineller Organe und Pathologien leisten

Two-dimensional ultrasound and ultrasound elastography imaging of trigger points in women with myofascial pain syndrome treated by acupuncture and electroacupuncture: a double-blinded randomized controlled pilot study

Chronic pain has been often associated with myofascial pain syndrome (MPS), which is determined by myofascial trigger points (MTrP). New features have been tested for MTrP diagnosis. The aim of this study was to evaluate two-dimensional ultrasonography (2D US) and ultrasound elastography (UE) images and elastograms of upper trapezius MTrP during electroacupuncture (EA) and acupuncture (AC) treatment. 24 women participated, aged between 20 and 40 years (M ± SD = 27.33 ± 5.05) with a body mass index ranging from 18.03 to 27.59 kg/m2 (22.59 ± 3.11), a regular menstrual cycle, at least one active MTrP at both right (RTPz) and left trapezius (LTPz) and local or referred pain for up to six months. Subjects were randomized into EA and AC treatment groups and the control sham AC (SHAM) group. Intensity of pain was assessed by visual analogue scale; MTrP mean area and strain ratio (SR) by 2D US and UE. A significant decrease of intensity in general, RTPz, and LTPz pain was observed in the EA group (p = 0.027; p < 0.001; p = 0.005, respectively) and in general pain in the AC group (p < 0.001). Decreased MTrP area in RTPz and LTPz were observed in AC (p < 0.001) and EA groups (RTPz, p = 0.003; LTPz, p = 0.005). Post-treatment SR in RTPz and LTPz was lower than pre-treatment in both treatment groups. 2D US and UE effectively characterized MTrP and surrounding tissue, pointing to the possibility of objective confirmation of subjective EA and AC treatment effects.372152167COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informação2011/12659-

MAGNETIC RESONANCE ELASTOGRAPHY FOR APPLICATIONS IN RADIATION THERAPY

Magnetic resonance elastography (MRE) is an imaging technique that combines mechanical waves and magnetic resonance imaging (MRI) to determine the elastic properties of tissue. Because MRE is non-invasive, there is great potential and interest for its use in the detection of cancer. The first part of this thesis concentrates on parameter optimization and imaging quality of an MRE system. To do this, we developed a customized quality assurance phantom, and a series of quality control tests to characterize the MRE system. Our results demonstrated that through optimizing scan parameters, such as frequency and amplitude, MRE could provide a good qualitative elastogram for targets with different elasticity values and dimensions. The second part investigated the feasibility of integrating MRE into radiation therapy (RT) workflow. With the aid of a tissue-equivalent prostate phantom (embedded with three dominant intraprostatic lesions (DILs)), an MRE-integrated RT framework was developed. This framework contains a comprehensive scan protocol including Computed Tomography (CT) scan, combined MRI/MRE scans and a Volumetric Modulated Arc Therapy (VMAT) technique for treatment delivery. The results showed that using the comprehensive information could boost the MRE defined DILs to 84 Gy while keeping the remainder of the prostate to 78 Gy. Using a VMAT based technique allowed us to achieve a highly conformal plan (conformity index for the prostate and combined DILs was 0.98 and 0.91). Based on our feasibility study, we concluded that MRE data can be used for targeted radiation dose escalation. In summary, this thesis demonstrates that MRE is feasible for applications in radiation oncology

Ultrasound Imaging

Ultrasound Imaging - Current Topics presents complex and current topics in ultrasound imaging in a simplified format. It is easy to read and exemplifies the range of experiences of each contributing author. Chapters address such topics as anatomy and dimensional variations, pediatric gastrointestinal emergencies, musculoskeletal and nerve imaging as well as molecular sonography. The book is a useful resource for researchers, students, clinicians, and sonographers looking for additional information on ultrasound imaging beyond the basics

Robust Displacement Estimation for Ultrasound Elastography and Thermal Imaging

Ultrasound imaging is becoming the modality of choice for many diagnostic and surgical procedures. Besides being inexpensive and safe, ultrasonography is emerging as a quantitative tool able to image tissue properties. In this dissertation we focus on elastography and thermal imaging, which both rely on the measurement of real or apparent motion in ultrasound image sequences. In ultrasound elastography, signal decorrelation is widely viewed as the major limiting factor for adoption of into clinical practice. In this dissertation we focus on improving the robustness of a displacement estimation method based on dynamic programming, addressing multiple weak points. We propose a set of tools which can improve its ability to overcome displacement discontinuities and regions of poorly correlated RF data. The method is further extended to three dimensional data. Phantom, animal and human studies are presented for experimental validation. The addition of robust tools results in an improved ability to achieve repeatable, artifact-free strain maps, without compromising computational speed. In thermal imaging, we focus on the estimation of real and apparent motion while the tissue temperature is increased in an ablation procedure. Estimating heat-induced echo shifts is a very difficult problem because of their very small amplitude, on the order of tens of microns. They can easily be masked by other sources of deformation/movement from the environment such as patient motion or hand tremor. In this dissertation, we build upon the robust displacement estimation method for elastography, with the additional deployment of an iterative motion compensation algorithm. The validation experiments are performed on laboratory induced ablation lesions, where the ultrasound probe is either held by the operator's hand or supported by a robotic arm. We demonstrate the ability to detect and remove non-heat induced tissue motion at every step of the ablation procedure. Our results exceed the state of the art in both the accuracy of temperature estimation as well as the length of time over which temperature estimation can be performed. Previous research in the area of motion compensation resulted in good results for experiments lasting less than 10 seconds. Our experiments lasted close to 20 minutes

In-vitro Strain and Modulus Measurements in Porcine Cervical Lymph Nodes

Cervical lymph nodes are common sites of metastatic involvement in head and neck cancers. These lymph nodes are superficially located and palpation is a common practice for assessing nodal hardness and staging cancer which is, however, too subjective and with limited accuracy. In this study, the mechanical properties of pig lymph node tissues were investigated using ultrasound elastography and indentation test. Lymph nodes were excised from fresh pork pieces and embedded in an agar-gelatin phantom for strain imaging by elastography. A strain ratio reflecting the strain contrast of lymph node over agar-gelatin phantom was used to assess the elasticity of the lymph node. A cutting device was then custom-designed to slice the phantom into uniform slices for indentation test. The measurements revealed that there were significant differences in both the strain ratio and Young’s modulus between the peripheral and middle regions of the lymph nodes (both p < 0.05); however, the results appeared contradictory. Correlation between the results of the two measurements (modulus ratio vs. inversed strain ratio) showed their association was moderate for both the peripheral and middle regions (R2 = 0.437 and 0.424 respectively). As the tests were only performed on normal lymph nodes, comparison in stiffness between healthy and abnormal lymph nodes could not be made. Future studies should be conducted to quantify the stiffness change in abnormal lymph nodes