A Mechatronic Cardiovascular Simulation System for Jugular Venous Echo-Doppler Training

Echo-doppler examination of the jugular vessel is a powerful tool for the early diagnosis of cardiovascular disorders that can be further related to central nervous system diseases. Unfortunately, the ultrasound technique is strongly operator-dependent, so the quality of the scan, the accuracy of the measurement, and therefore the rapidity and robustness of the diagnosis reflect the degree of training. The paper presents the development of a mechatronic simulation system for improving the skill of novice physicians in echo-doppler procedures. The patient is simulated by a silicone manikin whose materials are designed to have a realistic ultrasound response. Two tubes allow blood-mimicking fluid to flow inside the manikin, simulating the hemodynamics of the internal jugular vein. The mechatronic system is designed for controlling the flow waveform, to reproduce several clinical cases of interest for diagnosis. The experiments investigate the accuracy of the echo-doppler measurements performed on the proposed system by novice operators using a real ultrasound scanner

Mri Methods For Imaging The Feto-Placental Vasculature And Blood

Fetal magnetic resonance imaging (MRI) in recent times has become a well-established adjunct to ultrasound (US) in routine clinical prenatal care and diagnostics. The majority of fetal MRI is restricted to T2-weighted scans, where the diagnosis is based on the appearance of normal and abnormal tissue. Although there have been many advancements in MRI and a plethora of sequences, that probe different anatomical and different physiological process, the adaptation of these in fetal imaging has been rather slow. Many of these can extract quantitative parameters that can throw light on the underlying tissue’s normal/patho-physiology. But the use of such quantitative MRI methods has been extremely limited in fetal imaging due to its unique and dynamic physiological milieu that pose several technical challenges including low signal to noise and/or resolution, artifacts associated with abdominal imaging and most importantly fetal motion. These limitations are expected to be overcome by (a) optimizing and (b) developing novel MR imaging sequences, both of which constitute the primary aim of my work. This work develops a framework that allows for vascular imaging in the fetus and placenta. This includes both qualitative vascular imaging and blood flow quantification. Towards this, three broad directions were explored (a) Moving to higher field imaging, while optimizing parameters for low energy deposition and (b) application of non-gated phase contrast MRI and (c) optimization of conventional time-of-flight angiography for fetal applications

OPTICAL COHERENCE TOMOGRAPHY FOR NEUROSURGEY AND CANCER RESEARCH

Optical Coherence Tomography (OCT) provides non-labeling, real-time and high resolution images, which has the potential to transform the paradigm of surgical guidance and preclinical animal studies. The design and development of OCT devices for neurosurgery guidance and novel imaging algorithms for monitoring anti-cancer therapy have been pursued in this work. A forward-imaging needle-type OCT probe was developed which can fit into minimally invasive tools (I.D. ~ 1mm), detect the at-risk blood vessels, and identify tissue micro-landmarks. This promising guidance tool improves the safety and the accuracy of needle-based procedures, which are currently performed without imaging feedback. Despite the great imaging capability, OCT is limited by the shallow imaging depth (1-2 mm). In order to address this issue, the first MRI compatible OCT system has been developed. The multi-scale and multi-contrast MRI/OCT imaging combination significantly improves the accuracy of intra-operative MRI by two orders (from 1mm to 0.01 mm). In contrast to imaging systems, a thin (0.125 mm), low-cost (1/10 cost of OCT system) and simple fiber sensor technology called coherence gated Doppler (CGD) was developed which can be integrated with many surgical tools and aid in the avoidance of intracranial hemorrhage. Furthermore, intra-vital OCT is a powerful tool to study the mechanism of anti-cancer therapy. Photo-immunotherapy (PIT) is a low-side-effect cancer therapy based on an armed antibody conjugate that induces highly selective cancer cell necrosis after exposure to near infrared light both in vitro and in vivo. With novel algorithms that remove the bulk motion and track the vessel lumen automatically, OCT reveals dramatic hemodynamic changes during PIT and helps to elucidate the mechanisms behind the PIT treatment. The transformative guidance tools and the novel image processing algorithms pave a new avenue to better clinical outcomes and preclinical animal studies

Real-time blood oxygenation tomography with multispectral photoacoustics

Multispectral photoacoustics is an emerging biomedical imaging modality which combines the penetration depth and resolution of high frequency medical ultrasonography with an optical absorption contrast. This enables tomographic imaging of blood oxygen saturation, a functional biomarker with wide applications. Already, photoacoustic imaging (PAI) is widely applied for small animal imaging in preclinical research. While PAI is a multiscale modality, its translation to clinical research and interventional use remains challenging. The objective of this thesis was to investigate the usefulness of multispectral PAI as a technique for interventional tomographic imaging of blood oxygenation. This thesis presents open challenges alongside research contributions to address them. These contributions are, (1) The design and implementation of an interventional PAI system, (2) Methods for real-time photoacoustic (PA) image processing and quantification of tissue absorption and blood oxygenation, and finally (3) the application of multispectral PAI to translational neurosurgical research – performing the first high spatiotemporal resolution tomography of spreading depolarization, and at the same time the first interventional PAI on any gyrencephalic (folded) brain. Such interventional imaging in neurology is one of many promising fields of application for PAI

TIME SERIES ANALYSIS AND CLUSTERING TO CHARACTERIZE CARDIORESPIRATORY INSTABILITY PATTERNS IN STEP-DOWN UNIT PATIENTS

Background: Cardiorespiratory instability (CRI) in noninvasively monitored step-down unit (SDU) patients has a variety of etiologies, and therefore likely manifests in different patterns of vital signs (VS) changes. Objective: We sought to describe differences in admission characteristics and outcomes between patients with and without CRI. We explored use of clustering techniques to identify VS patterns within initial CRI epoch (CRI1) and assessed inter-cluster differences in admission characteristics, outcomes and medications. Methods: Admission characteristics and continuous monitoring data (frequency 1/20 Hz) were recorded in 307 patients. Vital sign (VS) deviations beyond local instability trigger criteria for 3 consecutive minutes or for 4 out of a 5 minute moving window were classified as CRI events. We identified CRI1 in 133 patients, derived statistical features of CRI1 epoch and employed hierarchical and k-means clustering techniques. We tested several clustering solutions and used 10-fold cross validation and ANOVA to establish best solution. Inter-cluster differences in admission characteristics, outcomes and medications were assessed. Main Results: Patients transferred to the SDU from units with higher monitoring capability were more likely to develop CRI (n=133, CRI 44% vs no CRI n=174, 31%, p=.042). Patients with at least one event of CRI had longer hospital length of stay (CRI 11.3 + 10.2 days vs no CRI 7.8 + 9.2, p=.001) and SDU unit stay (CRI 6.1 + 4.9 days vs no CRI 3.5 + 2.9, p< .001). Four main clusters(C) were derived. Clusters were significantly different based on age (p=0.001; younger patients in C1 and older in C2), number of comorbidities (p<0.01; more C2 patients had ≥2), and admission source (p=0.008; more C1 and C4 patients transferred in from a higher intensity monitoring unit). Patients with CRI differed significantly (p<.05) from those without CRI based on medication categories. Conclusions: CRI1 was associated with prolonged hospital and SDU length of stay. Patients transferred from a higher level of care were more likely to develop CRI, suggesting that they are sicker. Future study will be needed to determine if there are common physiologic underpinnings of VS clusters which might inform monitoring practices and clinical decision-making when CRI first manifests

Developing a non-invasive treatment for twin-twin transfusion syndrome using high intensity focused ultrasound in an animal model

High Intensity Focused Ultrasound (HIFU) is a non-invasive, non-ionising technology which can selectively occlude blood vessels. In Twin-Twin Transfusion Syndrome (TTTS), anastomotic placental vessels in a shared placenta allow uneven blood distribution between the twins. Despite advances in prenatal and neonatal care, TTTS remains the leading cause of death and disability in twins. Invasive fetoscopic laser can divide anastomoses, with risks of miscarriage, placental haemorrhage, extreme prematurity or second trimester rupture of membranes. Fetoscopic laser has undergone improvements in technology and therapeutic protocols over two decades, but it still does not consistently improve survival or decrease severe neurological morbidity in surviving twins. Hence, it is only used in severe cases, where benefits outweigh risks, and over 16-18 weeks gestation, after chorion and amnion fusion. This represents an unmet clinical need, which could be addressed by ultrasound-guided HIFU (USgHIFU). Selective occlusion of placental vessels using HIFU has not been described. Ultrasound identification of placental vascular anastomoses in humans is described, but is not in routine clinical use. Therefore, we tested the efficacy and safety of using USgHIFU as a non-invasive method of placental vascular occlusion in the pregnant sheep. An iterative study design in six animal groups was used. Treatment protocols for ultrasound guidance and HIFU delivery were developed in three animal groups. The efficacy and rates of associated direct and indirect iatrogenic harm of each version of the protocol was tested in another three animal groups, using invasive and non-invasive measures. Overall, transdermal USgHIFU occluded 97% of target placental vessels in the most developed treatment protocol. This persisted for 21 days and showed evidence of permanent vessel occlusion by fibrosis obliterans. This was achieved without significant adverse events, although maternal skin (2%), uterine (1%) and fetal skin burns (1%) were observed. There were no long term effects (up to 21 d) of the technique based on assessment of maternal and fetal cardiovascular, metabolic, endocrine and obstetric outcomes, or evidence of fetal compromise. This study is proof of principle that USgHIFU can be used to occlude placental vessels in the pregnant sheep. There is a low rate of direct iatrogenic harm and no evidence of indirect harm associated with the technique. As such, this supports the concept of future translational studies to develop USgHIFU as a treatment for TTTS in humans.Open Acces