scholarly journals A practical method for multimodal registration and assessment of whole-brain disease burden using PET, MRI, and optical imaging

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Matthew L. Scarpelli ◽  
Debbie R. Healey ◽  
Shwetal Mehta ◽  
Vikram D. Kodibagkar ◽  
Christopher C. Quarles
Keyword(s):  
Optical Imaging ◽  
Imaging System ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Neurological Diseases ◽  
Spatial Scales ◽  
Phenotypic Heterogeneity ◽  
Tissue Slices ◽  
Rodent Brain

Abstract Many neurological diseases present with substantial genetic and phenotypic heterogeneity, making assessment of these diseases challenging. This has led to ineffective treatments, significant morbidity, and high mortality rates for patients with neurological diseases, including brain cancers and neurodegenerative disorders. Improved understanding of this heterogeneity is necessary if more effective treatments are to be developed. We describe a new method to measure phenotypic heterogeneity across the whole rodent brain at multiple spatial scales. The method involves co-registration and localized comparison of in vivo radiologic images (e.g. MRI, PET) with ex vivo optical reporter images (e.g. labeled cells, molecular targets, microvasculature) of optically cleared tissue slices. Ex vivo fluorescent images of optically cleared pathology slices are acquired with a preclinical in vivo optical imaging system across the entire rodent brain in under five minutes, making this methodology practical and feasible for most preclinical imaging labs. The methodology is applied in various examples demonstrating how it might be used to cross-validate and compare in vivo radiologic imaging with ex vivo optical imaging techniques for assessing hypoxia, microvasculature, and tumor growth.

scholarly journals In vivo imaging of swimming micromotors using hybrid high-frequency ultrasound and photoacoustic imaging

2020 ◽  
Author(s):  
Azaam Aziz ◽  
Joost Holthof ◽  
Sandra Meyer ◽  
Oliver G. Schmidt ◽  
Mariana Medina-Sánchez
Keyword(s):  
High Frequency ◽  
Imaging System ◽  
Ex Vivo ◽  
Photoacoustic Imaging ◽  
Imaging Techniques ◽  
High Frequency Ultrasound ◽  
Living Organisms ◽  
And Function ◽  
Frequency Ultrasound

AbstractThe fast evolution of medical micro- and nanorobots in the endeavor to perform non-invasive medical operations in living organisms boosted the use of diverse medical imaging techniques in the last years. Among those techniques, photoacoustic (PA) tomography has shown to be promising for the imaging of microrobots in deep-tissue (ex vivo and in vivo), as it possesses the molecular specificity of optical techniques and the penetration depth of ultrasound imaging. However, the precise maneuvering and function control of microrobots, in particular in living organisms, demand the combination of both anatomical and functional imaging methods. Therefore, herein, we report the use of a hybrid High-Frequency Ultrasound (HFUS) and PA imaging system for the real-time tracking of magnetically driven micromotors (single and swarms) in phantoms, ex vivo, and in vivo (in mice bladder and uterus), envisioning their application for targeted drug-delivery.

scholarly journals In Vivo and Ex Vivo Microscopy: Moving Toward the Integration of Optical Imaging Technologies Into Pathology Practice

2018 ◽  
Vol 143 (3) ◽  
pp. 288-298 ◽  
Author(s):  
Wendy A. Wells ◽  
Michael Thrall ◽  
Anastasia Sorokina ◽  
Jeffrey Fine ◽  
Savitri Krishnamurthy ◽  
...  
Keyword(s):  
Optical Imaging ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Clinical Care ◽  
Imaging Data ◽  
Imaging Technologies ◽  
Optical Images ◽  
Tissue Removal ◽  
Excised Tissue

The traditional surgical pathology assessment requires tissue to be removed from the patient, then processed, sectioned, stained, and interpreted by a pathologist using a light microscope. Today, an array of alternate optical imaging technologies allow tissue to be viewed at high resolution, in real time, without the need for processing, fixation, freezing, or staining. Optical imaging can be done in living patients without tissue removal, termed in vivo microscopy, or also in freshly excised tissue, termed ex vivo microscopy. Both in vivo and ex vivo microscopy have tremendous potential for clinical impact in a wide variety of applications. However, in order for these technologies to enter mainstream clinical care, an expert will be required to assess and interpret the imaging data. The optical images generated from these imaging techniques are often similar to the light microscopic images that pathologists already have expertise in interpreting. Other clinical specialists do not have this same expertise in microscopy, therefore, pathologists are a logical choice to step into the developing role of microscopic imaging expert. Here, we review the emerging technologies of in vivo and ex vivo microscopy in terms of the technical aspects and potential clinical applications. We also discuss why pathologists are essential to the successful clinical adoption of such technologies and the educational resources available to help them step into this emerging role.

scholarly journals QuantitativeIn VivoDetection ofChlamydia muridarumAssociated Inflammation in a Mouse Model Using Optical Imaging

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Manishkumar Patel ◽  
Shu-An Lin ◽  
Melissa A. Boddicker ◽  
Christopher DeMaula ◽  
Brett Connolly ◽  
...  
Keyword(s):  
Mouse Model ◽  
Optical Imaging ◽  
Imaging System ◽  
Ex Vivo ◽  
Statistical Significance ◽  
Transmitted Disease ◽  
Chlamydia Infection ◽  
Imaging Biomarker ◽  
Chlamydia Muridarum

Chlamydia trachomatisis a bacterial sexually transmitted disease with over 1.3 million cases reported to the CDC in 2010. While Chlamydia infection is easily treated with antibiotics, up to 70% of infections are asymptomatic and go untreated. The current mouse model relies on invasive upper genital tract gross pathology readouts at ~60–80 days postinfection. High throughput optical imaging through the use of biomarkers has been successfully used to quickly evaluate several disease processes. Here we evaluate Neutrophil Elastase 680 (Elastase680) for its ability to measureChlamydia muridarumassociated inflammation in live mice using fluorescence molecular tomography (FMT) andIn VivoImaging System (IVIS). Optical imaging was able to distinguish with statistical significance between vaccinated and nonvaccinated mice as well as mock-challenged and challenged mice 2 weeks after challenge which was 9 weeks sooner than typical gross pathological assessment. Immunohistochemistry confirmed the presence of neutrophils and correlated well with bothin vivoandex vivoimaging. In this report we demonstrate that Elastase680 can be used as a molecular imaging biomarker for inflammation associated with chlamydial infection in a mouse model and that these biomarkers can significantly decrease the time for pathology evaluation and thus increase the rate of therapeutics discovery.

scholarly journals Optical angiography for diabetes-induced pathological changes in microvascular structure and function: An overview

2021 ◽  
Author(s):  
Jingtan Zhu ◽  
Dongyu Li ◽  
Tingting Yu ◽  
Dan Zhu
Keyword(s):  
Optical Imaging ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Valuable Insight ◽  
Pathological Changes ◽  
Vascular Networks ◽  
Functional Changes ◽  
Chronic Hyperglycemia ◽  
Organ Systems

Diabetes mellitus (DM) is a kind of metabolic disorder characterized by chronic hyperglycemia and glucose intolerance due to absolute or relative lack of insulin, leading to chronic damage of vasculature within various organ systems. These detrimental effects on the vascular networks will result in the development of various diseases associated with microvascular injury. Modern optical imaging techniques provide essential tools for accurate evaluation of the structural and functional changes of blood vessels down to capillaries level, which can offer valuable insight on understanding the development of DM-associated complications and design of targeted therapy. This review will briefly introduce the DM-induced structural and functional alterations of vasculature within different organs such as skin, cerebrum and kidneys, as well as how novel optical imaging techniques facilitate the studies focusing on exploration of these pathological changes of vasculature caused by DM both in-vivo and ex-vivo.

scholarly journals Performance of a novel protease-activated fluorescent imaging system for intraoperative detection of residual breast cancer during breast conserving surgery

2021 ◽  
Vol 187 (1) ◽  
pp. 145-153
Author(s):  
Conor R. Lanahan ◽  
Bridget N. Kelly ◽  
Michele A. Gadd ◽  
Michelle C. Specht ◽  
Carson L. Brown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real Time ◽  
Imaging System ◽  
Ex Vivo ◽  
Menopausal Status ◽  
Fluorescent Imaging ◽  
Cancer Subtypes ◽  
Surgical Workflow ◽  
Tumor Types

Abstract Purpose Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20–40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact on surgical workflow and performance across patient and tumor types. Methods We performed IRB-approved, prospective, non-randomized studies in breast cancer lumpectomy procedures. The LUM Imaging System uses LUM015, a protease-activated fluorescent imaging agent that identifies residual tumor in the surgical cavity walls. Fluorescent cavity images were collected in real-time and analyzed using system software. Results Cavity and specimen images were obtained in 55 patients injected with LUM015 at 0.5 or 1.0 mg/kg and in 5 patients who did not receive LUM015. All tumor types were distinguished from normal tissue, with mean tumor:normal (T:N) signal ratios of 3.81–5.69. T:N ratios were 4.45 in non-dense and 4.00 in dense breasts (p = 0.59) and 3.52 in premenopausal and 4.59 in postmenopausal women (p = 0.19). Histopathology and tumor receptor testing were not affected by LUM015. Falsely positive readings were more likely when tumor was present < 2 mm from the adjacent specimen margin. LUM015 signal was stable in vivo at least 6.5 h post injection, and ex vivo at least 4 h post excision. Conclusions Intraoperative use of the LUM Imaging System detected all breast cancer subtypes with robust performance independent of menopausal status and breast density. There was no significant impact on histopathology or receptor evaluation.

scholarly journals A Tumbling Magnetic Microrobot System for Biomedical Applications

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 861
Author(s):  
Elizabeth E. Niedert ◽  
Chenghao Bi ◽  
Georges Adam ◽  
Elly Lambert ◽  
Luis Solorio ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Biomedical Applications ◽  
Imaging System ◽  
Ex Vivo ◽  
Negative Control ◽  
Circular Path ◽  
Rotational Axis ◽  
Significant Difference

A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

scholarly journals Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic loci in orthotopic neuroblastoma model

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiao-Le Yu ◽  
Shing Chan ◽  
Marcus Kwong-Lam Fung ◽  
Godfrey Chi-Fung Chan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Primary Tumor ◽  
Imaging System ◽  
Ex Vivo ◽  
Tumor Formation ◽  
Human Neuroblastoma Cell ◽  
Fluorescence Signal ◽  
Human Neuroblastoma

Abstract Background Majority of neuroblastoma patients develop metastatic disease at diagnosis and their prognosis is poor with current therapeutic approach. Major challenges are how to tackle the mechanisms responsible for tumorigenesis and metastasis. Human mesenchymal stem cells (hMSCs) may be actively involved in the constitution of cancer microenvironment. Methods An orthotopic neuroblastoma murine model was utilized to mimic the clinical scenario. Human neuroblastoma cell line SK-N-LP was transfected with luciferase gene, which were inoculated with/without hMSCs into the adrenal area of SCID-beige mice. The growth and metastasis of neuroblastoma was observed by using Xenogen IVIS 100 in vivo imaging and evaluating gross tumors ex vivo. The homing of hMSCs towards tumor was analyzed by tracing fluorescence signal tagged on hMSCs using CRI Maestro™ imaging system. Results hMSCs mixed with neuroblastoma cells significantly accelerated tumor growth and apparently enhanced metastasis of neuroblastoma in vivo. hMSCs could be recruited by primary tumor and also become part of the tumor microenvironment in the metastatic lesion. The metastatic potential was consistently reduced in lung and tumor when hMSCs were pre-treated with stromal cell derived factor-1 (SDF-1) blocker, AMD3100, suggesting that the SDF-1/CXCR4 axis was one of the prime movers in the metastatic process. Conclusions hMSCs accelerated and facilitated tumor formation, growth and metastasis. Furthermore, the homing propensity of hMSCs towards both primary tumor and metastatic loci can also provide new therapeutic insights in utilizing bio-engineered hMSCs as vehicles for targeted anti-cancer therapy.

scholarly journals In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

2005 ◽  
Vol 4 (4) ◽  
pp. 7290.2005.05133 ◽  
Author(s):  
Matthew J. Hardwick ◽  
Ming-Kai Chen ◽  
Kwamena Baidoo ◽  
Martin G. Pomper ◽  
Tomás R. Guilarte
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Benzodiazepine Receptors ◽  
Small Animal ◽  
Small Animal Pet ◽  
Planar Imaging ◽  
Peripheral Benzodiazepine Receptors

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

scholarly journals Proof of concept of a multimodal intravital molecular imaging system for tumour transpathology investigation

2021 ◽  
Author(s):  
Zhen Liu ◽  
Tao Cheng ◽  
Stephan Düwel ◽  
Ziying Jian ◽  
Geoffrey J. Topping ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Imaging System ◽  
Ex Vivo ◽  
Fiducial Markers ◽  
Proof Of Concept ◽  
Registration Accuracy ◽  
Microscopic Imaging ◽  
Window Chamber

Abstract Background Transpathology highlights the interpretation of the underlying physiology behind molecular imaging. However, it remains challenging due to the discrepancies between in vivo and in vitro measurements and difficulties of precise co-registration between trans-scaled images. This study aims to develop a multimodal intravital molecular imaging (MIMI) system as a tool for in vivo tumour transpathology investigation. Methods The proposed MIMI system integrates high-resolution positron imaging, magnetic resonance imaging (MRI) and microscopic imaging on a dorsal skin window chamber on an athymic nude rat. The window chamber frame was designed to be compatible with multimodal imaging and its fiducial markers were customized for precise physical alignment among modalities. The co-registration accuracy was evaluated based on phantoms with thin catheters. For proof of concept, tumour models of the human colorectal adenocarcinoma cell line HT-29 were imaged. The tissue within the window chamber was sectioned, fixed and haematoxylin–eosin (HE) stained for comparison with multimodal in vivo imaging. Results The final MIMI system had a maximum field of view (FOV) of 18 mm × 18 mm. Using the fiducial markers and the tubing phantom, the co-registration errors are 0.18 ± 0.27 mm between MRI and positron imaging, 0.19 ± 0.22 mm between positron imaging and microscopic imaging and 0.15 ± 0.27 mm between MRI and microscopic imaging. A pilot test demonstrated that the MIMI system provides an integrative visualization of the tumour anatomy, vasculatures and metabolism of the in vivo tumour microenvironment, which was consistent with ex vivo pathology. Conclusions The established multimodal intravital imaging system provided a co-registered in vivo platform for trans-scale and transparent investigation of the underlying pathology behind imaging, which has the potential to enhance the translation of molecular imaging.

scholarly journals EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Erik H. J. G. Aarntzen ◽  
Edel Noriega-Álvarez ◽  
Vera Artiko ◽  
André H. Dias ◽  
Olivier Gheysens ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Radionuclide Imaging ◽  
Musculoskeletal Diseases ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Large Body ◽  
Therapeutic Interventions ◽  
Histopathological Analysis ◽  
Complementary Value

AbstractInflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.

Sign in / Sign up

Export Citation Format

Share Document