Co-registration of pre-operative CT with ex vivo surgically excised ground glass nodules to define spatial extent of invasive adenocarcinoma on in vivo imaging: a proof-of-concept study

Abstract Purpose Local recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery. Methods In five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo. Results In all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (FImean), with SNIP tissue showing a median FImean of 77.54 (IQR 50.47–112.30) compared to 35.99 (IQR 21.48–57.81) in uninvolved tissue (p < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78. Conclusions A fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery. Trial registration NCT03925285.

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GFP-Aequorin Protein Sensor for Ex Vivo and In Vivo Imaging of Ca 2+ Dynamics in High-Ca 2+ Organelles

Cell Chemical Biology ◽

10.1016/j.chembiol.2016.05.010 ◽

2016 ◽

Vol 23 (6) ◽

pp. 738-745 ◽

Cited By ~ 22

Author(s):

Paloma Navas-Navarro ◽

Jonathan Rojo-Ruiz ◽

Macarena Rodriguez-Prados ◽

María Dolores Ganfornina ◽

Loren L. Looger ◽

...

Keyword(s):

In Vivo Imaging ◽

Ex Vivo ◽

Protein Sensor

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In vivo assessment of neuroinflammation in progressive multiple sclerosis: a proof of concept study with [18F]DPA714 PET

Journal of Neuroinflammation ◽

10.1186/s12974-018-1352-9 ◽

2018 ◽

Vol 15 (1) ◽

Cited By ~ 11

Author(s):

Marloes H. J. Hagens ◽

Sandeep V. Golla ◽

Martijn T. Wijburg ◽

Maqsood Yaqub ◽

Dennis Heijtel ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Multiple Sclerosis ◽

Proof Of Concept ◽

Concept Study ◽

In Vivo Assessment

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Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas

PLoS ONE ◽

10.1371/journal.pone.0149387 ◽

2016 ◽

Vol 11 (2) ◽

pp. e0149387 ◽

Cited By ~ 26

Author(s):

David Kryza ◽

Frédéric Debordeaux ◽

Laurent Azéma ◽

Aref Hassan ◽

Olivier Paurelle ◽

...

Keyword(s):

In Vivo Imaging ◽

Ex Vivo ◽

Matrix Metalloprotease

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More efficient exchange of sickle red blood cells can be achieved by exchanging the densest red blood cells: An ex vivo proof of concept study

Transfusion and Apheresis Science ◽

10.1016/j.transci.2018.12.005 ◽

2019 ◽

Vol 58 (1) ◽

pp. 100-106

Author(s):

Suzanne R. Thibodeaux ◽

Yvette C. Tanhehco ◽

Leah Irwin ◽

Lita Jamensky ◽

Kevin Schell ◽

...

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Ex Vivo ◽

Proof Of Concept ◽

Concept Study ◽

Sickle Red Blood Cells

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Ex vivo measurement of tissue distribution of a nitroxide radical after intravenous injection and its in vivo imaging using a rapid scan ESR-CT system

Magnetic Resonance Imaging ◽

10.1016/s0730-725x(99)00122-8 ◽

2000 ◽

Vol 18 (2) ◽

pp. 151-156 ◽

Cited By ~ 16

Author(s):

Hitoshi Togashi ◽

Taku Matsuo ◽

Haruhide Shinzawa ◽

Yoshio Takeda ◽

Li Shao ◽

...

Keyword(s):

Tissue Distribution ◽

Intravenous Injection ◽

In Vivo Imaging ◽

Ex Vivo ◽

Nitroxide Radical ◽

Rapid Scan ◽

Ct System

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

Molecular Imaging ◽

10.2310/7290.2005.05133 ◽

2005 ◽

Vol 4 (4) ◽

pp. 7290.2005.05133 ◽

Cited By ~ 19

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.

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In Vivo Molecular Imaging Using Low-Boiling-Point Phase-Change Contrast Agents: A Proof of Concept Study

Ultrasound in Medicine & Biology ◽

10.1016/j.ultrasmedbio.2018.08.004 ◽

2019 ◽

Vol 45 (1) ◽

pp. 177-191 ◽

Cited By ~ 9

Author(s):

Juan D. Rojas ◽

Paul A. Dayton

Keyword(s):

Molecular Imaging ◽

Phase Change ◽

Contrast Agents ◽

Boiling Point ◽

Proof Of Concept ◽

Concept Study

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

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05574-y ◽

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.

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