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Purpose: Lutetium-177-Dotatate (Lutathera ® ) is a combined radionuclide-peptide that is FDA-approved for the treatment of well-differentiated, somatostatin receptor-positive, gastroenteropancreatic neuroendocrine tumors. Carcinoid crisis is a rare, but potentially life-threatening risk of this radiopharmaceutical, of which prompt recognition and treatment is essential to reducing morbidity. This manuscript provides an overview of the topic to promote awareness of this adverse event, with emphasis on early recognition and management. In addition, we present our institution's experience with Lutetium-177-Dotatate-associated complications across a five-year period., Methods: A literature review of lutetium-177-dotatate therapy and its potential implication of carcinoid crisis was performed. Additionally, a review of our institution's experience is presented., Results: The incidence of carcinoid crisis induced by Lutetium-177-Dotatate therapy is estimated to range between 1 and 2% of treatment recipients. Those who have tumors located within the midgut, higher tumor burden, and the presence of metastasis have an increased risk of developing carcinoid crisis, among other risk factors. Carcinoid crisis is most often encountered within 12-48 h of receiving the first treatment dose, with the most common symptoms being nausea/vomiting, flushing, and diarrhea., Conclusion: Carcinoid crisis is a rare but potentially life-threatening complication of Lutetium-177-Dotatate therapy. Knowledge of risk factors and prompt recognition of symptoms is essential to successful treatment, with early initiation of intravenous octreotide serving a critical step in reducing morbidity of this adverse event., (© 2024. The Author(s).)

Primary progressive aphasia (PPA) is a disease known to affect the frontal and temporal regions of the left hemisphere. PPA is often an indication of future development of dementia, specifically semantic dementia (SD) for frontotemporal dementia (FTD) and logopenic progressive aphasia (LPA) as an atypical presentation of Alzheimer's disease (AD). The purpose of this review is to clarify the value of 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-positron emission tomography (PET) in the detection and diagnosis of PPA. A comprehensive review of literature was conducted using Web of Science, PubMed, and Google Scholar. The three PPA subtypes show distinct regions of hypometabolism in FDG-PET imaging with SD in the anterior temporal lobes, LPA in the left temporo-parietal junction, and nonfluent/agrammatic Variant PPA (nfvPPA) in the left inferior frontal gyrus and insula. Despite the distinct patterns, overlapping hypometabolic areas can complicate differential diagnosis, especially in patients with SD who are frequently diagnosed with AD. Integration with other diagnostic tools could refine the diagnostic process and lead to improved patient outcomes. Future research should focus on validating these findings in larger populations and exploring the therapeutic implications of early, accurate PPA diagnosis with more targeted therapeutic interventions., (© 2024. The Author(s).)

Purpose: To evaluate a recently developed technique using intraoperative optical coherence tomography (OCT) to measure subretinal tissue plasminogen activator (tPA) volumes in patients with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD). Methods: Three patients (72 to 83 years old) had 25-gauge pars plana vitrectomy, subretinal tPA, and a partial gas fill. An investigational intraoperative OCT system with a modified widefield noncontact indirect viewing apparatus was used to image subretinal tPA blebs. Using the recently developed technique, the volume and surface area in the segmented region of interest were determined. Results: In each case, the delivered tPA volume measured from the syringe differed from the intraoperative OCT-measured subretinal tPA volume: Patient 1, 130 µL from syringe, 118 µL based on intraoperative OCT, 9% difference; Patient 2, 140 µL, 50 µL, 64%; Patient 3, 110 µL, 122 µL, 11%. The total bleb surface area was 129 mm 2 in Patient 1, 55 mm 2 in Patient 2, and 106 mm 2 in Patient 3. Conclusions: This was the first human study to implement and evaluate intraoperative OCT image-based methods to obtain volumetric bleb measurements in patients receiving subretinal tPA for exudative AMD. This proof-of-concept study showed that intraoperative OCT-obtained bleb volume differed from intraoperative recordings, which could be explained by tPA delivery into the vitreous, efflux through the retinotomy, or human error. Intraoperative OCT can provide visualization and quantification of subretinal tPA bleb volume and surface area, which has implications for improved safety, efficacy, and analysis of the effects of subretinal drug delivery., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Vajzovic has received research funding from Heidelberg Engineering Inc, Orbit Biomedical Inc, Novartis, and Second Sight Inc and has served as a consultant to AERI, Alcon, Alimera Sciences, Allergan, Bausch + Lomb, DORC, Genentech, Guidepoint, Janssen Pharmaceutical, Orbit Biomedical, and Second Sight. Dr. Toth receives royalties through her university from Alcon. Dr. Toth has owner equity and salary in Theia Imaging, LLC. Dr. Vajzovic, Dr. Toth, Mr. Li, Mr. Raynor, and Dr. Izatt have unlicensed and pending patents related to the investigational device and imaging in this study. Dr. Izatt receives royalties through Duke University from Leica Microsystems Inc and has served as a consultant to Alcon., (© The Author(s) 2024.)

Background/purpose: Visualization of peripheral retinal structures with optical coherence tomography (OCT) can be challenging but can offer valuable clinical information. We describe a method for intraoperative OCT of the peripheral retina., Methods: An investigational microscope-integrated OCT system with real-time 4D volumetric imaging was used in conjunction with a Goldmann style mirrored contact lens intraoperatively to capture peripheral images in three patients., Results: We identified retinoschisis, a retinal break, and areas of focal retinal detachment using our peripheral OCT method., Conclusion: Use of a Goldmann lens in conjunction with intraoperative OCT offers surgeons the ability to resolve peripheral pathology that cannot be easily evaluated with OCT otherwise.

Ophthalmic microsurgery is traditionally performed using stereomicroscopes and requires visualization and manipulation of sub-millimeter tissue structures with limited contrast. Optical coherence tomography (OCT) is a non-invasive imaging modality that can provide high-resolution, depth-resolved cross sections, and has become a valuable tool in clinical practice in ophthalmology. While there has been substantial progress in both research and commercialization efforts to bring OCT imaging into live surgery, its use is still somewhat limited due to factors such as low imaging speed, limited scan configurations, and suboptimal data visualization. In this paper we describe, to the best of our knowledge, the translation of the fastest swept-source intraoperative OCT system with real-time volumetric imaging with stereoscopic data visualization provided via a heads-up display into the operating room. Results from a sampling of human anterior segment and retinal surgeries chosen from 93 human surgeries using the system are shown and the benefits that this mode of intrasurgical OCT imaging provides are discussed., Competing Interests: AD: Duke University (P), CZ: Duke University (P), CAT: Duke University Medical Center (P), Alcon Laboratories (R), Theia Imaging (I,C), Emmes (C), LMV: Duke University Medical Center (P), Alcon Inc. (F,C), JAI: Duke University (P), (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

4D-microscope-integrated optical coherence tomography (4D-MIOCT) is an emergent multimodal imaging technology in which live volumetric OCT (4D-OCT) is implemented in tandem with standard stereo color microscopy. 4D-OCT provides ophthalmic surgeons with many useful visual cues not available in standard microscopy; however it is challenging for the surgeon to effectively integrate cues from simultaneous-but-separate imaging in real-time. In this work, we demonstrate progress towards solving this challenge via the fusion of data from each modality guided by segmented 3D features. In this way, a more readily interpretable visualization that combines and registers important cues from both modalities is presented to the surgeon., Competing Interests: RT: Duke University (P), CV: Duke University (P), JDL: Duke University (P), WR: Duke University Medical Center (P), AD: Duke University (P), Leica Microsystems (P, R), Alcon Inc. (C), LV: Duke University Medical Center (P), AK: Duke University Medical Center (P), Leica Microsystems (P), CT: Duke University Medical Center (P), Alcon Inc. (R), Emmes Inc. (C), Theia Imaging LLC (I), JAI: Duke University (P), Leica Microsystems (P, R), Alcon Inc. (C)., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Intraoperative optical coherence tomography (OCT) systems provide high-resolution, real-time visualization and/or guidance of microsurgical procedures. While the use of intraoperative OCT in ophthalmology has significantly improved qualitative visualization of surgical procedures inside the eye, new surgical techniques to deliver therapeutics have highlighted the lack of quantitative information available with current-generation intraoperative systems. Indirect viewing systems used for retinal surgeries introduce distortions into the resulting OCT images, making it particularly challenging to make calibrated quantitative measurements. Using an intraoperative OCT system based in part on the Leica Enfocus surgical microscope interface, we have devised novel measurement procedures, which allowed us to build optical and mathematical models to perform validation of quantitative measurements of intraocular structures for intraoperative OCT. These procedures optimize a complete optical model of the sample arm including the OCT scanner, viewing attachments, and the patient's eye, thus obtaining the voxel pitch throughout an OCT volume and performing quantitative measurements of the dimensions of imaged objects within the operative field. We performed initial validation by measuring objects of known size in a controlled eye phantom as well as ex vivo porcine eyes. The technique was then extended to measure other objects and structures in ex vivo porcine eyes and in vivo human eyes., Competing Interests: JDL: Duke University (P), WR: Duke University Medical Center (P), AD: Duke University (P), CZ: Duke University (P), CAT: Duke University Medical Center (P), Alcon Laboratories (R) LMV: Duke University Medical Center (P), Alcon Inc. (F,C), JAI: Duke University (P), (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Applications of various positron emission tomography (PET) tracers for assessing atherosclerosis have been evolving over the years. 18 F-fluorodeoxyglucose (FDG)-PET was introduced in 2001 as a probe for this purpose. During the past decade, numerous papers have described a major role for sodium 18 F-fluoride (NaF) as another tracer for assessing this vascular disease. We have reviewed the existing data about the merits of both techniques for assessing atherosclerosis. We have to emphasize that our team has been actively involved in conducting research with both tracers over many years. In this review, we have relied upon the data from the CAMONA study which has become a gold standard for defining the role of PET imaging in atherosclerosis. This study was one of the largest of any in recent years and has allowed comprehensive comparison between these two tracers in detecting and quantifying atherosclerosis. Based on what we have learned from this major undertaking, we believe the role of FDG-PET will be limited in assessing atherosclerosis in clinical work-up. This is relevant to both major and coronary arteries. In contrast to NaF-PET, the role of FDG-PET in assessing coronary artery atherosclerosis is almost non-existent. Based on the existing data in this domain, NaF-PET is an ideal imaging modality for both research and clinical assessment of atherosclerosis. The aim of this review is to describe the pros and cons of both approaches based on the existing data in the literature., Competing Interests: None., (AJNMMI Copyright © 2021.)

The force required for trocar insertion in hypotonous eyes can cause significant deformation of the globe and result in an iatrogenic injury to the lens, posterior capsule, or retina from the sharp trocar tip. We developed a device designed to stabilize the globe and provide counterpressure without significant globe deformation during trocar insertion. Our novel device was modeled using computer-aided design software, three-dimensional (3D) printed, and validated in an ex vivo porcine model. The risk of trocar-retinal touch was evaluated by comparing the distance between the trocar tip and opposing retina with either a cotton swab or our 3D printed device. We found an increased distance between the retina and trocar tip at the time of trocar insertion using our novel device: 3.3 ± 1.3 mm (P = 0.035), suggesting an improved safety margin. This device has the potential to improve the safety of trocar insertion in eyes at risk of trocar-associated injury, including hypotonous, previously vitrectomized, and nanophthalmic eyes., Competing Interests: None

Purpose: To investigate the use of imaging modalities in the volumetric measurement of the subretinal space and examine the volume of subretinal blebs created by a subretinal drug delivery device utilizing microscope-integrated optical coherence tomography (MIOCT)., Methods: An MIOCT image-based volume measurement method was developed and assessed for accuracy and reproducibility by imaging ceramic spheres of known size that were surgically implanted into ex vivo porcine eyes. This method was then used to measure subretinal blebs created in 10 porcine eyes by injection of balanced salt solution utilizing a subretinal delivery device via a suprachoroidal cannula. Bleb volumes obtained from MIOCT were compared to the intended injection volume., Results: Validation of image-based volume measurements of ceramic spheres showed accuracy to ±0.029 µL (5.6%) for objects imaged over the posterior pole and ±0.025 µL (4.8%) over peripheral retina. The mean expected injection volume from extraocular tests of the suprachoroidal cannula was 66.44 µL (σ = 2.4 µL). The mean injection volume as measured by the MIOCT imaging method was 54.8 µL (σ = 12.3 µL), or 82.48% of expected injection volume., Conclusions: MIOCT can measure the volume of subretinal blebs with accuracy and precision. The novel suprachoroidal approach using a subretinal delivery device was able to deliver greater than 80% of expected injection volume into the subretinal space, as assessed by MIOCT., Translational Relevance: MIOCT provides a method for visualization, and analysis of images enables surgeons to quantify and evaluate the success of subretinal drug delivery via a suprachoroidal approach.

Purpose: Subretinal injections of therapeutics are commonly used to treat ocular diseases. Accurate dosing of therapeutics at target locations is crucial but difficult to achieve using subretinal injections due to leakage, and there is no method available to measure the volume of therapeutics successfully administered to the subretinal location during surgery. Here, we introduce the first automatic method for quantifying the volume of subretinal blebs, using porcine eyes injected with Ringer's lactate solution as samples., Design: Ex vivo animal study., Methods: Microscope-integrated optical coherence tomography was used to obtain 3D visualization of subretinal blebs in porcine eyes at Duke Eye Center. Two different injection phases were imaged and analyzed in 15 eyes (30 volumes), selected from a total of 37 eyes. The inclusion/exclusion criteria were set independently from the algorithm-development and testing team. A novel lightweight, deep learning-based algorithm was designed to segment subretinal bleb boundaries. A cross-validation method was used to avoid selection bias. An ensemble-classifier strategy was applied to generate final results for the test dataset., Results: The algorithm performs notably better than 4 other state-of-the-art deep learning-based segmentation methods, achieving an F1 score of 93.86 ± 1.17% and 96.90 ± 0.59% on the independent test data for entry and full blebs, respectively., Conclusion: The proposed algorithm accurately segmented the volumetric boundaries of Ringer's lactate solution delivered into the subretinal space of porcine eyes with robust performance and real-time speed. This is the first step for future applications in computer-guided delivery of therapeutics into the subretinal space in human subjects., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To compare the repeatability and reproducibility of axial and lateral retinal measurements using handheld optical coherence tomography (OCT) systems and a tabletop OCT system., Methods: Graders measured central foveal thickness (CFT), optic nerve-to-fovea distance (OFD), and retinal nerve fiber layer (RNFL) thickness on OCT scans of the right eye of 10 healthy adults. Three OCT systems were used: handheld Leica Envisu, investigational handheld swept-source OCT (UC3), and Heidelberg Spectralis tabletop system. All eyes were imaged five times with each OCT system by each of two imagers. A components of variance analysis provided estimates of repeatability (variation due to random error) and reproducibility (variation due to imager, grader, and random error) expressed as standard deviation and (coefficient of variation %)., Results: Repeatability of CFT (µm) for Envisu, UC3, and Spectralis was 5.9 (2.6%), 6.9 (2.9%), and 4.7 (2.1%), and the reproducibility was 6.1 (2.7%), 7.3 (3.1%), and 4.7 (2.1%), respectively. The repeatability of OFD (mm) was 0.13 (2.9%), 0.10 (2.3%), and 0.07 (1.6%), and the reproducibility was 0.13 (3.0%), 0.10 (2.3%), and 0.07 (1.6%,) respectively. The repeatability for RNFL thickness (µm) for Envisu, UC3, and Spectralis was 4.3 (7.8%), 2.7 (5.4%), and 2.9 (4.9%), and the reproducibility was 4.5 (8.3%), 2.9 (5.8%), and 2.9 (4.9%), respectively., Conclusions: All three OCT systems had good repeatability and reproducibility with coefficients of variation of less than 3.5% for CFT and OFD measurements, and less than 8.5% for RNFL thickness., Translational Relevance: Our findings inform the repeatability and reproducibility of retinal axial and lateral measurements on handheld OCT and are useful for both clinical research and patient care., Competing Interests: Disclosure: X. Chen, None; V. Tai, None; B. McGeehan, None; G.-S. Ying, None; C. Viehland, Theia Imaging, L.L.C. (I); R. Imperio, None; K.P. Winter, None; W. Raynor, None; D. Tran-Viet, None; S. Mangalesh, None; M.G. Maguire, None; C.A. Toth, Theia Imaging, L.L.C. (I), (Copyright 2020 The Authors.)

Introduction: Several radiolabeled somatostatin analogues have been developed for molecular imaging of neuroendocrine tumors (NETs) with single-photon emission computed tomography (SPECT) and positron-emission tomography (PET). The aim of the present study was to report our first results using 64 Cu-DOTATOC in patients with NETs., Methods: Thirty-three patients with NETs (15 female, 18 male; mean age 64 ± 13 years) were included in this retrospective study. 64 Cu-DOTATOC PET-CT scans were performed on all patients., Results: Five out of 33 patients with a history of NET after surgical removal of the primary lesion showed no pathological lesions on PET-CT imaging and 8/33 patients had enhanced uptake in the area of recurrent meningioma at the skull base. The remaining 20/33 patients had a history of neuroendocrine tumor in the gastrointestinal tract (GEP-NET) and were presented with at least one pathological lesion., Conclusion: The high detection rate of suspected lesions in patients with NETs and the high target-to-background contrast found in this study hold promise for the safe application of 64 Cu-DOTATOC in patients with NET.

Medical imaging plays a particularly important role in the care of elderly patients, in whom complex symptomatology and a high prevalence of musculoskeletal diseases necessitate sensitive imaging modalities. MRI is the most commonly used imaging modality in the evaluation of various musculoskeletal disorders. The integration of positron emission technique and computed tomography as well as magnetic resonance imaging allows for generating complimentary data for accurate and quantitative diagnosis. This article highlights the implementations of molecular imaging probes in the assessment of prevalent musculoskeletal disorders among geriatric population with emphasis on osteoarthritis, osteoporosis, diabetic foot, and prosthetic joint infections. We also discuss the sensitivity of FDG-PET imaging in differentiating polymyalgia rheumatica from other diseases that have similar clinical presentation., (Copyright © 2018. Published by Elsevier Inc.)

Objective: The aim of this study was to describe osseous metabolic activity with respect to age and weight in the spine as expressed through fluorine-18-sodium fluoride (F-NaF) uptake in a healthy male population., Participants and Methods: Whole-body F-NaF PET/CT scans of healthy male participants (22-71 years, 50-145 kg, n=47) were analysed using a global assessment methodology to derive the mean standardized uptake values (SUVmean). Individual regions of the spine (cervical, thoracic and lumbar) along with the aggregate whole spine were assessed and compared as potential functions of age and body weight., Results: Older participants did not have higher F-NaF uptake than younger participants (whole spine, P=0.93; cervical, P=0.12, thoracic, P=0.93; lumbar, P=0.42), whereas increasing body weight was associated with greater tracer uptake (whole spine P=0.003; cervical P=0.01; thoracic P=0.002; lumbar P=0.004). Both the thoracic (average SUVmean=4.864±1.338) and lumbar (average SUVmean=4.939±1.284) spines had significantly elevated (P≤0.0001) uptake compared with the cervical spine (average SUVmean=3.969±1.024)., Conclusion: We assessed the metabolic activity of the spine's osseous tissues with F-NaF PET using a global assessment approach in healthy men. Our study provides evidence of differences in spinal metabolism as related to weight, but not age. Our study offers a foundation for future larger studies in symptomatic populations.

Objective: This study aimed to explore the age and weight-related metabolic trends in the spines of healthy male subjects using fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) imaging., Subjects and Methods: Forty three healthy male subjects (age 23-75 years, weight 50-145kg) were selected from the CAMONA study. A global assessment methodology was applied to the subjects' 18 F-FDG 180 minute scans, where each region of the spine (cervical, thoracic and lumbar) was individually encapsulated in a single region of interest, and standardized uptake value (SUVmean) was calculated per respective region., Results: SUVmean increased significantly with weight in both the thoracic spine (Slope=0.0066, P=0.001) and lumbar spine (Slope=0.0087, P<0.0001), but not the cervical spine. There were no significant correlations between age and SUVmean in all three regions. The cervical spine (average SUVmean=1.84±0.31) illustrated elevated activity when compared to the thoracic (average SUVmean=1.46±0.27, P<0.0001) and lumbar (average SUVmean=1.41±0.28, P<0.0001) spines., Conclusion: This study illustrated the ability of 18 F-FDG PET to assess metabolic processes in the spine. The data provided evidence of weight dependent metabolic activity, likely related to inflammation. This study offers a methodological precedent that can be applied to studies in populations with back pain.

(18)F-sodium fluoride (NaF) as an imaging tracer portrays calcium metabolic activity either in the osseous structures or in soft tissue. Currently, clinical use of NaF-PET is confined to detecting metastasis to the bone, but this approach reveals indirect evidence for disease activity and will have limited use in the future in favor of more direct approaches that visualize cancer cells in the read marrow where they reside. This has proven to be the case with FDG-PET imaging in most cancers. However, a variety of studies support the application of NaF-PET to assess benign osseous diseases. In particular, bone turnover can be measured from NaF uptake to diagnose osteoporosis. Several studies have evaluated the efficacy of bisphosphonates and their lasting effects as treatment for osteoporosis using bone turnover measured by NaF-PET. Additionally, NaF uptake in vessels tracks calcification in the plaques at the molecular level, which is relevant to coronary artery disease. Also, NaF-PET imaging of diseased joints is able to project disease progression in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Further studies suggest potential use of NaF-PET in domains such as back pain, osteosarcoma, stress-related fracture, and bisphosphonate-induced osteonecrosis of the jaw. The critical role of NaF-PET in disease detection and characterization of many musculoskeletal disorders has been clearly demonstrated in the literature, and these methods will become more widespread in the future. The data from PET imaging are quantitative in nature, and as such, it adds a major dimension to assessing disease activity.