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During the past five decades neurosurgery has made great progress, with marked improvements in patient outcomes. These noticeable improvements of morbidity and mortality can be attributed to the advances in innovative technologies used in neurosurgery. Cutting-edge technologies are essential in most neurosurgical procedures, and there is no doubt that neurosurgery

During the past five decades neurosurgery has made great progress, with marked improvements in patient outcomes. These noticeable improvements of morbidity and mortality can be attributed to the advances in innovative technologies used in neurosurgery. Cutting-edge technologies are essential in most neurosurgical procedures, and there is no doubt that neurosurgery has become heavily technology dependent. With the introduction of any new modalities, surgeons must adapt, train, and become thoroughly familiar with the capabilities and the extent of application of these new innovations. Within the past decade, endoscopy has become more widely used in neurosurgery, and this newly adopted technology is being recognized as the new minimally invasive future of neurosurgery. The use of endoscopy has allowed neurosurgeons to overcome common challenges, such as limited illumination and visualization in a very narrow surgical corridor; however, it introduces other challenges, such as instrument "sword fighting" and limited maneuverability (surgical freedom). The newly introduced concept of surgical freedom is very essential in surgical planning and approach selection and can play a role in determining outcome of the procedure, since limited surgical freedom can cause fatigue or limit the extent of lesion resection. In my thesis, we develop a consistent objective methodology to quantify and evaluate surgical freedom, which has been previously evaluated subjectively, and apply this model to the analysis of various endoscopic techniques. This model is crucial for evaluating different endoscopic surgical approaches before they are applied in a clinical setting, for identifying surgical maneuvers that can improve surgical freedom, and for developing endoscopic training simulators that accurately model the surgical freedom of various approaches. Quantifying the extent of endoscopic surgical freedom will also provide developers with valuable data that will help them design improved endoscopes and endoscopic instrumentation.
ContributorsElhadi, Ali M. (Author) / Preul, Mark C (Thesis advisor) / Towe, Bruce (Thesis advisor) / Little, Andrew S. (Committee member) / Nakaji, Peter (Committee member) / Vu, Eric T (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo

Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI) of local drug delivery is performed to visualize and quantify the time resolved distribution of MRI contrast agents. I find it is possible to visualize contrast agent distributions in near real time from local delivery vehicles using MRI. Three dimensional T1 maps are processed to produce in vivo concentration maps of contrast agent for individual animal models. The method for obtaining concentration maps is analyzed to estimate errors introduced at various steps in the process. The method is used to evaluate different controlled release vehicles, vehicle placement, and type of surgical wound in rabbits as a model for antimicrobial delivery to orthopaedic infection sites. I are able to see differences between all these factors; however, all images show that contrast agent remains fairly local to the wound site and do not distribute to tissues far from the implant in therapeutic concentrations. I also produce a mathematical model that investigates important mechanisms in the transport of antimicrobials in a wound environment. It is determined from both the images and the mathematical model that antimicrobial distribution in an orthopaedic wounds is dependent on both diffusive and convective mechanisms. Furthermore, I began development of MRI visible therapeutic agents to examine active drug distributions. I hypothesize that this work can be developed into a non-invasive, patient specific, clinical tool to evaluate the success of interventional procedures using local drug delivery vehicles.
ContributorsGiers, Morgan (Author) / Caplan, Michael R (Thesis advisor) / Massia, Stephen P (Committee member) / Frakes, David (Committee member) / McLaren, Alex C. (Committee member) / Vernon, Brent L (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Rapid intraoperative diagnosis of brain tumors is of great importance for planning treatment and guiding the surgeon about the extent of resection. Currently, the standard for the preliminary intraoperative tissue analysis is frozen section biopsy that has major limitations such as tissue freezing and cutting artifacts, sampling errors, lack of

Rapid intraoperative diagnosis of brain tumors is of great importance for planning treatment and guiding the surgeon about the extent of resection. Currently, the standard for the preliminary intraoperative tissue analysis is frozen section biopsy that has major limitations such as tissue freezing and cutting artifacts, sampling errors, lack of immediate interaction between the pathologist and the surgeon, and time consuming.

Handheld, portable confocal laser endomicroscopy (CLE) is being explored in neurosurgery for its ability to image histopathological features of tissue at cellular resolution in real time during brain tumor surgery. Over the course of examination of the surgical tumor resection, hundreds to thousands of images may be collected. The high number of images requires significant time and storage load for subsequent reviewing, which motivated several research groups to employ deep convolutional neural networks (DCNNs) to improve its utility during surgery. DCNNs have proven to be useful in natural and medical image analysis tasks such as classification, object detection, and image segmentation.

This thesis proposes using DCNNs for analyzing CLE images of brain tumors. Particularly, it explores the practicality of DCNNs in three main tasks. First, off-the shelf DCNNs were used to classify images into diagnostic and non-diagnostic. Further experiments showed that both ensemble modeling and transfer learning improved the classifier’s accuracy in evaluating the diagnostic quality of new images at test stage. Second, a weakly-supervised learning pipeline was developed for localizing key features of diagnostic CLE images from gliomas. Third, image style transfer was used to improve the diagnostic quality of CLE images from glioma tumors by transforming the histology patterns in CLE images of fluorescein sodium-stained tissue into the ones in conventional hematoxylin and eosin-stained tissue slides.

These studies suggest that DCNNs are opted for analysis of CLE images. They may assist surgeons in sorting out the non-diagnostic images, highlighting the key regions and enhancing their appearance through pattern transformation in real time. With recent advances in deep learning such as generative adversarial networks and semi-supervised learning, new research directions need to be followed to discover more promises of DCNNs in CLE image analysis.
ContributorsIzady Yazdanabadi, Mohammadhassan (Author) / Preul, Mark (Thesis advisor) / Yang, Yezhou (Thesis advisor) / Nakaji, Peter (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Transorbital surgery has gained recent notoriety due to its incorporation into endoscopic skull base surgery. The body of published literature on the field is cadaveric and observation. The pre-clinical studies are focused on the use of the endoscope only. Furthermore the methodology utilised in the published literature is inconsistent and

Transorbital surgery has gained recent notoriety due to its incorporation into endoscopic skull base surgery. The body of published literature on the field is cadaveric and observation. The pre-clinical studies are focused on the use of the endoscope only. Furthermore the methodology utilised in the published literature is inconsistent and does not embody the optimal principles of scientific experimentation. This body of work evaluates a minimally invasive novel surgical corridor - the transorbital approach - its validity in neurosurgical practice, as well as both qualitatively and quantitatively assessing available technological advances in a robust experimental fashion. While the endoscope is an established means of visualisation used in clinical transorbital surgery, the microscope has never been assessed with respect to the transorbital approach. This question is investigated here and the anatomical and surgical benefits and limitations of microscopic visualisation demonstrated. The comparative studies provide increased knowledge on specifics pertinent to neurosurgeons and other skull base specialists when planning pre-operatively, such as pathology location, involved anatomical structures, instrument maneuvrability and the advantages and disadvantages of the distinct visualisation technologies. This is all with the intention of selecting the most suitable surgical approach and technology, specific to the patient, pathology and anatomy, so as to perform the best surgical procedure. The research findings illustrated in this body of work are diverse, reproducible and applicable. The transorbital surgical corridor has substantive potential for access to the anterior cranial fossa and specific surgical target structures. The neuroquantitative metrics investigated confirm the utility and benefits specific to the respective visualisation technologies i.e. the endoscope and microscope. The most appropriate setting wherein the approach should be used is also discussed. The transorbital corridor has impressive potential, can utilise all available technological advances, promotes multi-disciplinary co-operation and learning amongst clinicians and ultimately, is a means of improving operative patient care.
ContributorsHoulihan, Lena Mary (Author) / Preul, Mark C. (Thesis advisor) / Vernon, Brent (Thesis advisor) / O' Sullivan, Michael G.J. (Committee member) / Lawton, Michael T. (Committee member) / Santarelli, Griffin (Committee member) / Smith, Brian (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Minimally invasive surgery is a surgical technique that is known for its reduced

patient recovery time. It is a surgical procedure done by using long reached tools and an

endoscopic camera to operate on the body though small incisions made near the point of

operation while viewing the live camera

Minimally invasive surgery is a surgical technique that is known for its reduced

patient recovery time. It is a surgical procedure done by using long reached tools and an

endoscopic camera to operate on the body though small incisions made near the point of

operation while viewing the live camera feed on a nearby display screen. Multiple camera

views are used in various industries such as surveillance and professional gaming to

allow users a spatial awareness advantage as to what is happening in the 3D space that is

presented to them on 2D displays. The concept has not effectively broken into the

medical industry yet. This thesis tests a multi-view camera system in which three cameras

are inserted into a laparoscopic surgical training box along with two surgical instruments,

to determine the system impact on spatial cognition, perceived cognitive workload, and

the overall time needed to complete the task, compared to one camera viewing the

traditional set up. The task is a non-medical task and is one of five typically used to train

surgeons’ motor skills when initially learning minimally invasive surgical procedures.

The task is a peg transfer and will be conducted by 30 people who are randomly assigned

to one of two conditions; one display and three displays. The results indicated that when

three displays were present the overall time initially using them to complete a task was

slower; the task was perceived to be completed more easily and with less strain; and

participants had a slightly higher performance rate.
ContributorsSchroll, Katelyn (Author) / Cooke, Nancy J. (Thesis advisor) / Chiou, Erin (Committee member) / Craig, Scotty (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Tissue approximation and repair have been performed with sutures and staples for centuries, but these means are inherently traumatic. Tissue repair using laser-responsive nanomaterials can lead to rapid tissue sealing and repair and is an attractive alternative to existing clinical methods. Laser tissue welding is a sutureless technique for sealing

Tissue approximation and repair have been performed with sutures and staples for centuries, but these means are inherently traumatic. Tissue repair using laser-responsive nanomaterials can lead to rapid tissue sealing and repair and is an attractive alternative to existing clinical methods. Laser tissue welding is a sutureless technique for sealing incised or wounded tissue, where chromophores convert laser light to heat to induce in tissue sealing. Introducing chromophores that absorb near-infrared light creates differential laser absorption and allows for laser wavelengths that minimizes tissue damage.

In this work, plasmonic nanocomposites have been synthesized and used in laser tissue welding for ruptured porcine intestine ex vivo and incised murine skin in vivo. These laser-responsive nanocomposites improved tissue strength and healing, respectively. Additionally, a spatiotemporal model has been developed for laser tissue welding of porcine and mouse cadaver intestine sections using near-infrared laser irradiation. This mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser welding. Finally, in a model of surgical site infection, laser-responsive nanomaterials were shown to be efficacious in inhibiting bacterial growth. By incorporating an anti-microbial functionality to laser-responsive nanocomposites, these materials will serve as a treatment modality in sealing tissue, healing tissue, and protecting tissue in surgery.
ContributorsUrie, Russell Ricks (Author) / Rege, Kaushal (Thesis advisor) / Acharya, Abhinav (Committee member) / DeNardo, Dale (Committee member) / Holloway, Julianne (Committee member) / Thomas, Marylaura (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Intraoperative diagnosis in neurosurgery has traditionally relied on frozen and formalin-fixed, paraffin-embedded section analysis of biopsied tissue samples. Although this technique is considered to be the “gold standard” for establishing a histopathologic diagnosis, it entails a number of significant limitations such as invasiveness and the time required for processing and

Intraoperative diagnosis in neurosurgery has traditionally relied on frozen and formalin-fixed, paraffin-embedded section analysis of biopsied tissue samples. Although this technique is considered to be the “gold standard” for establishing a histopathologic diagnosis, it entails a number of significant limitations such as invasiveness and the time required for processing and interpreting the tissue. Rapid intraoperative diagnosis has become possible with a handheld confocal laser endomicroscopy (CLE) system. Combined with appropriate fluorescent stains or labels, CLE provides an imaging technique for real-time intraoperative visualization of histopathologic features of the suspected tumor and healthy tissues.

This thesis scrutinizes CLE technology for its ability to provide real-time intraoperative in vivo and ex vivo visualization of histopathological features of the normal and tumor brain tissues. First, the optimal settings for CLE imaging are studied in an animal model along with a generational comparison of CLE performance. Second, the ability of CLE to discriminate uninjured normal brain, injured normal brain and tumor tissues is demonstrated. Third, CLE was used to investigate cerebral microvasculature and blood flow in normal and pathological conditions. Fourth, the feasibility of CLE for providing optical biopsies of brain tumors was established during the fluorescence-guided neurosurgical procedures. This study established the optimal workflow and confirmed the high specificity of the CLE optical biopsies. Fifth, the feasibility of CLE was established for endoscopic endonasal approaches and interrogation of pituitary tumor tissue. Finally, improved and prolonged near wide-field fluorescent visualization of brain tumor margins was demonstrated with a scanning fiber endoscopy and 5-aminolevulinic acid.

These studies suggested a novel paradigm for neurosurgery-pathology workflow when the noninvasive intraoperative optical biopsies are used to interrogate the tissue and augment intraoperative decision making. Such optical biopsies could shorten the time for obtaining preliminary information on the histological composition of the tissue of interest and may lead to improved diagnostics and tumor resection. This work establishes a basis for future in vivo optical biopsy use in neurosurgery and planning of patient-related outcome studies. Future studies would lead to refinement and development of new confocal scanning technologies making noninvasive optical biopsy faster, convenient and more accurate.
ContributorsBelykh, Evgenii (Author) / Preul, Mark C (Thesis advisor) / Vernon, Brent (Thesis advisor) / Nakaji, Peter (Committee member) / Stabenfeldt, Sarah E (Committee member) / Arizona State University (Publisher)
Created2020