OPTICAL COHERENCE TOMOGRAPHY OPHTHALMIC SURGICAL GUIDANCE

Optical coherence tomography (OCT) performs high-resolution cross-sectional and volumetric tissue imaging in situ through the combination of confocal gating, coherence gating, and polarization gating. Because it is noninvasive, OCT has been used in multiple clinical applications such as tissue pathology assessment and interventional procedure guidance. Moreover, OCT can perform functional measurements such as phase-sensitive measurement of blood flow and polarization-sensitive measurement of tissue birefringence. These features made OCT one of the most widely used imaging systems in ophthalmology. In this thesis, we present several novel OCT methods developed for microsurgery guidance and OCT image analysis. The thesis mainly consists of five parts, which are shown as follows. First, we present a BC-mode OCT image visualization method for microsurgery guidance, where multiple sparsely sampled B-scans are combined to generate a single cross-sectional image with an enhanced instrument and tissue layer visibility and reduced shadowing artifacts. The performance of the proposed method is demonstrated by guiding a 30-gauge needle into an ex-vivo human cornea. Second, we present a microscope-integrated OCT guided robotic subretinal injection method. A workflow is designed for accurate and stable robotic needle navigation. The performance of the proposed method is demonstrated on ex-vivo porcine eye subretinal injection. Third, we present optical flow OCT technique that quantifies accurate velocity fields. The accuracy of the proposed method is verified through phantom flow experiments by using a diluted milk powder solution as the scattering medium, in both cases of advective flow and turbulent flow. Fourth, we present a wrapped Gaussian mixture model to stabilize the phase of swept source OCT systems. A closed-form iteration solution is derived using the expectation-maximization algorithm. The performance of the proposed method is demonstrated through ex-vivo, in-vivo, and flow phantom experiments. The results show its robustness in different application scenarios. Fifth, we present a numerical landmark localization algorithm based on a convolutional neural network and a conditional random field. The robustness of the proposed method is demonstrated through ex-vivo porcine intestine landmark localization experiments

On Finite Difference Jacobian Computation in Deformable Image Registration

Producing spatial transformations that are diffeomorphic has been a central problem in deformable image registration. As a diffeomorphic transformation should have positive Jacobian determinant $|J|$ everywhere, the number of voxels with $|J|<0$ has been used to test for diffeomorphism and also to measure the irregularity of the transformation. For digital transformations, $|J|$ is commonly approximated using central difference, but this strategy can yield positive $|J|$'s for transformations that are clearly not diffeomorphic -- even at the voxel resolution level. To show this, we first investigate the geometric meaning of different finite difference approximations of $|J|$. We show that to determine diffeomorphism for digital images, use of any individual finite difference approximations of $|J|$ is insufficient. We show that for a 2D transformation, four unique finite difference approximations of $|J|$'s must be positive to ensure the entire domain is invertible and free of folding at the pixel level. We also show that in 3D, ten unique finite differences approximations of $|J|$'s are required to be positive. Our proposed digital diffeomorphism criteria solves several errors inherent in the central difference approximation of $|J|$ and accurately detects non-diffeomorphic digital transformations

Late Neoarchean crust-mantle geodynamics : evidence from Pingquan Complex of the Northern Hebei Province, North China Craton

This study is financially supported by the National Natural Science Foundation of China (Grant Nos. 41530207, 41502179, 41472165, 41602198) and Central University Basic Scientific Research Business Expenses (Grant No. 2652015038). PAC acknowledges support from Australian Research Council grant FL160100168.A late Neoarchean intra-oceanic arc along the northwestern margin of Eastern Block (EB), North China Craton, provides important insights into the nature of Archean mantle sources and crust-mantle geodynamics. The Pingquan Complex and the entire Northern Hebei Province (NHB) are located in the middle part of the arc, and overlap the northern extent of the Trans-North China Orogen. Zircon U-Pb isotopic age data reveal that the Pingquan Complex consists of ∼2537-2515 Ma dioritic gneisses, ∼2506-2503 Ma amphibolites, and ∼2491 Ma quartz monzodioritic to monzogranitic gneisses, and they show dominantly positive zircon εHf(t) (-0.6-+5.4) that are lower than coeval model depleted mantle values. Geochemical data for the Pingquan rocks and synchronous metabasalts and granitoid gneisses of Huai’an-Xuanhua and Dantazi complexes in the NHB are integrated. Except for the monzogranitic gneisses that were derived from partial melting of juvenile metagreywackes, the other rocks of the Pingquan Complex were derived from a metasomatized lithospheric mantle, and subjected to variable fractionation of clinopyroxene, hornblende and plagioclase, without significant crustal contamination. Moderately depleted zircon εHf(t), and high Sm/Hf and Nb/Ta (mostly of 1.34-3.96 and 15.50-32.58) suggest that the lithospheric mantle was enriched by subducted pelagic sediments metamorphosed to rutile-bearing eclogites before melting. Late Neoarchean crust-mantle geodynamic processes in the NHB are reconstructed. Intra-oceanic subduction initiated offshore of the northwestern margin of the EB at ∼2.55 Ga or earlier. Partial melting of slab basalts occurred at ∼2542-2499 Ma, with the melts contaminated by mantle wedge materials forming TTGs. Meanwhile, the sub-arc lithospheric mantle was enriched by fluids and melts released from slab basalts and pelagic sediments, and partial melting of this moderately depleted mantle generated ∼2537-2503 Ma diorites and basalts. Following final accretion of the arc onto the continental margin of the EB, the slab rollback/breakoff and asthenospheric mantle upwelling triggered partial melting of the metasomatized lithospheric mantle and crustal anatexis, generating ∼2491 Ma quartz monzodioritic and monzogranitic rocks. Accordingly, the NHB records Neoarchean crustal growth linked to oceanic subduction and arc-continent accretion, and highlights the importance of resolving the nature of mantle sources and crust-mantle interactions in understanding Archean crustal growth and evolution.PostprintPeer reviewe

Cyclic formation and stabilization of Archean lithosphere by accretionary orogenesis : constraints from TTG and potassic granitoids, North China Craton

This study is financially supported by the National Natural Science Foundation of China (Grant Nos. 41502179, 41530207, 41472165) and Central University Basic Scientific Research Business Expenses of China University of Geosciences (Beijing) (Grant No. 2652015038). PAC acknowledges support from Australian Research Council grant FL160100168.Accretionary orogens are major sites of modern continental growth, yet their role in the development of Archean continental crust remains enigmatic. Diverse granitoid suites from tonalite-trondhjemite-granodiorite (TTG) to potassic granitoids appeared during late Archean, representing a period of major continental formation and stabilization. In this study, whole-rock geochemical and zircon U-Pb and Lu-Hf isotopic data are reported for Neoarchean granitoid gneisses from the Northern Liaoning Terrane, northeastern North China Craton (NCC). Older granitoid gneisses (~2592-2537 Ma) define three magmatic zones migrating from southeast to northwest, each showing a common magmatic evolution from high-pressure TTGs to medium-/low-pressure TTGs and potassic granitoids. They have depleted zircon ƐHf(t) of +0.5 to +8.7. Younger ~2529-2503 Ma potassic granitoids and TTGs occur throughout the terrane, which are marked by variable zircon ƐHf(t) of -4.7 to +8.1, and are coeval with regional high grade metamorphism. Petrogenetic modeling and changing Sr/Y and (La/Yb)N of the granitoids suggest that the crust experienced episodic thickening and thinning, and became progressively evolved through development of potassic granitoids and sedimentary successions. The metavolcanic basement to the granitoids display tholeiitic to calc-alkaline affinities, together with the top-to-the-northwest thrusting and associated VMS-type Cu-Zn deposits, suggesting cyclic crustal formation of Northern Liaoning within an accretionary orogen with a SE-dipping subduction polarity. Cyclic crustal thickening and thinning is related to tectonic switching from advancing to retreating relations between the downgoing and overriding plate. After ~2530 Ma, this accretionary system accreted to the ancient continental nucleus of NCC (Anshan-Benxi Terrane), signifying final lithosphere stabilization.Publisher PDFPeer reviewe

Late Neoarchean subduction-related crustal growth in the Northern Liaoning region of the North China Craton : evidence from ∼2.55-2.50 Ga granitoid gneisses

This study is financially supported by the National Natural Science Foundation of China (Grant Nos. 41272209, 41472165, 41502179, 41530207) and the Central University Basic Scientific Research Business Expenses of China University of Geosciences (Beijing) (Grant No. 2652015038).The North China Craton (NCC), dominated by ∼2.6-2.5 Ga tectonothermal events, provides a natural laboratory to study Neoarchean crustal growth and geodynamic evolution. Late Neoarchean granitoid gneisses are well exposed in the Northern Liaoning Province, located north of the ancient Anshan-Benxi terrane along the northeastern margin of the Eastern Block (EB) of the NCC. LA-ICPMS zircon U-Pb isotopic dating reveal that granitoid gneisses in the Qingyuan area can be grouped into two major episodes, i.e., ∼2559-2534 Ma strongly gneissic quartz dioritic and tonalitic to trondhjemitic gneisses; and ∼2529-2495 Ma weakly gneissic to massive quartz monzodioritic and monzogranitic gneisses, with subordinate tonalitic to trondhjemitic gneisses. The late magmatic episode was accompanied by regionally high-grade metamorphism (∼2510-2495 Ma). Most granitoid gneisses display highly depleted zircon εHf(t2) values (+4.2-+8.1), whereas one monzogranitic gneiss shows negative values of -4.7 to -1.0, indicating late Neoarchean crustal growth with minor involvement of ancient continental materials probably sourced from the Anshan-Benxi terrane. Geochemical and petrogenetic studies reveal that the quartz dioritic magmas were derived from partial melting of plagioclase-poor garnet amphibolites or eclogites metamorphosed from oceanic slab materials, with slab melts contaminated by mantle wedge peridotites during ascent. The tonalitic to trondhjemitic magmas stemmed from partial melting of mainly juvenile metabasaltic rocks with minor metagreywackes of lower arc crust. In comparison, the quartz monzodioritic and monzogranitic magmas were derived respectively from partial melting of depleted mantle sources metasomatized by slab-derived fluids and metagreywackes with different crustal resident ages at middle to lower crustal levels. Combined with previous studies of metavolcanic rocks, the Northern Liaoning Province records late Neoarchean crustal growth, evolving from mid-ocean ridge, through initiation and maturation of an intra-oceanic arc, to arc-continent collision. Arc-continent accretion and possibly slab rollback processes may have triggered reworking of both juvenile arc crust and minor ancient continental margin materials, generating the magmatic precursors for the monzogranitic gneisses. Overall, the intense late Neoarchean crustal growth of the EB was controlled mainly by arc-continent accretion, possibly linked to global assembly of cratonic fragments.PostprintPeer reviewe

Deep Learning Guided Autonomous Retinal Surgery using a Robotic Arm, Microscopy, and iOCT Imaging

Recent technological advancements in retinal surgery has led to the modern operating room consisting of a surgical robot, microscope, and intraoperative optical coherence tomography (iOCT). The integration of these tools raises the fundamental question of how to effectively combine them to enable surgical autonomy. In this work, we address this question by developing a unified framework that enables real-time autonomous surgical workflows utilizing the aforementioned devices. To achieve this, we make the following contributions: (1) we develop a novel imaging system that integrates microscopy and iOCT in real-time, accomplished by dynamically tracking the surgical instrument via a small iOCT scanning region (e.g. B-scan), which was not previously possible; (2) implementing various convolutional neural networks (CNN) that automatically segment and detect task-relevant information for surgical autonomy; (3) enabling surgeons to intuitively select goal waypoints within both the microscope and iOCT views through simple mouse-click interactions; (4) integrating model predictive control (MPC) for real-time trajectory generation that respects kinematic constraints to ensure patient safety. We show the utility of our system by tackling subretinal injection (SI), a challenging procedure that involves inserting a microneedle below the retinal tissue for targeted drug delivery, a task surgeons find challenging due to requiring tens-of-micrometers of accuracy and precise depth perception. We validate our system by conducting 30 successful SI trials on pig eyes, achieving needle insertion accuracy of $26 \pm 12 \mu m$ to various subretinal goals and duration of $55 \pm 10.8$ seconds. Preliminary comparisons to a human operator performing SI in robot-assisted mode highlight the enhanced safety of our system.Comment: pending submission to a journa

A Survey on Deep Learning in Medical Image Registration: New Technologies, Uncertainty, Evaluation Metrics, and Beyond

Over the past decade, deep learning technologies have greatly advanced the field of medical image registration. The initial developments, such as ResNet-based and U-Net-based networks, laid the groundwork for deep learning-driven image registration. Subsequent progress has been made in various aspects of deep learning-based registration, including similarity measures, deformation regularizations, and uncertainty estimation. These advancements have not only enriched the field of deformable image registration but have also facilitated its application in a wide range of tasks, including atlas construction, multi-atlas segmentation, motion estimation, and 2D-3D registration. In this paper, we present a comprehensive overview of the most recent advancements in deep learning-based image registration. We begin with a concise introduction to the core concepts of deep learning-based image registration. Then, we delve into innovative network architectures, loss functions specific to registration, and methods for estimating registration uncertainty. Additionally, this paper explores appropriate evaluation metrics for assessing the performance of deep learning models in registration tasks. Finally, we highlight the practical applications of these novel techniques in medical imaging and discuss the future prospects of deep learning-based image registration

Case Report: Isolated facial and trigeminal nerve palsy without ataxia in anti-GQ1b antibody syndrome secondary to Mycoplasma pneumonia

The presence of anti-GQ1b antibodies in serum or cerebrospinal fluid is a diagnostic indicator of the Miller–Fisher variant of Guillain–Barré syndrome (GBS), whereas anti-GQ1b antibody syndrome is rarely presented as acute bilateral pain in the cheeks and masticatory muscle fatigue without ophthalmoplegia, ataxia, or limb weakness. Here, we report a case of a female patient diagnosed with GBS characterized only by the involvement of the facial and trigeminal nerves who was positive for serum anti-GQ1b antibodies secondary to Mycoplasma pneumoniae infection. The patient was treated with macrolide antibiotics and neurotrophic drugs, and her symptoms were significantly alleviated after 1 month. This case indicates a new clinical presentation of GBS and anti-GQ1b antibody syndrome with a differential diagnosis of multiple cranial nerve damage of which neurological physicians should be aware. Positive anti-GQ1b antibodies secondary to infection were observed in this case, and antibiotic treatment resulted in a favorable prognosis. The specific underlying mechanism requires further investigation

Identification of differentially expressed microRNAs and the potential of microRNA-455-3p as a novel prognostic biomarker in glioma.

Glioma is an aggressive central nervous system malignancy. MicroRNAs (miRNAs/miRs) have been reported to be involved in the tumorigenesis of numerous types of cancer, including glioma. The present study aimed to identify the differentially expressed miRNAs in glioma, and further explore the clinical value of miR-455-3p in patients with glioma. GEO2R was used for the identification of the differentially expressed miRNAs according to the miRNA expression profiles obtained from the Gene Expression Omnibus database. OncomiR was used to analyze the relationship of miRNAs with the survival outcomes of the patients with glioma. A total of 108 patients with glioma were recruited to examine the expression levels of miR-455-3p and further explore its clinical value. The bioinformatics analysis results suggested that a total of 64 and 48 differentially expressed miRNAs were identified in the GSE90603 and GSE103229 datasets, respectively. There were 12 miRNAs in the overlap of the two datasets, of which three were able to accurately predict overall cancer survival, namely hsa-miR-7-5p, hsa-miR-21-3p and hsa-miR-455-3p. In patients with glioma, miR-455-3p was determined to be significantly upregulated (P<0.001). Additionally, patients with high miR-455-3p expression had significantly lower 5-year overall survival than those with low miR-455-3p expression (log-rank test, P=0.001). Cox regression analysis further determined that miR-455-3p was an independent prognostic indicator for overall survival in patients with glioma (hazard ratio=2.136; 95% CI=1.177-3.877; P=0.013). In conclusion, the present study revealed a series of miRNAs with potential functional roles in the pathogenesis of glioma, and provides findings that indicate miR-455-3p as a promising biomarker for the prognosis of glioma

ILT4 drives B7-H3 expression via PI3K/AKT/mTOR signalling and ILT4/B7-H3 co-expression correlates with poor prognosis in non-small cell lung cancer

AbstractImmunoglobulin-like transcript (ILT) 4 is critical for the inhibitory function of certain immune cells. We previously demonstrated that ILT4 is over-expressed in human non-small cell lung cancer (NSCLC) cells and is involved in tumour evasion via an unknown mechanism. In this report, we demonstrate that ILT4 increases the expression of the co-inhibitory molecule B7-H3 through PI3K/AKT/mTOR signalling. In primary human NSCLC tissues, a significant positive relationship is observed between ILT4 and B7-H3 expression. ILT4/B7-H3 co-expression is significantly associated with a reduction in T infiltrating lymphoid cells and lower overall survival. In summary, ILT4 increases B7-H3 expression and ILT4/B7-H3 co-expression may be involved in NSCLC progression