Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
Using Pre-Clinical Imaging to Detect Cancer

Using Pre-Clinical Imaging to Detect Cancer

Please can you tell us a bit about Photon’s etc preclinical infrared imagers? What sets them apart from others on the market?

Photon Etc.’s (IR VIVO™) system is the first and only turnkey hyperspectral preclinical imager optimized for imaging in the second biological window of the infrared (NIR-II) / short-wavelength infrared (SWIR) range available on the market to our knowledge.

Our product portfolio includes different components of this preclinical imager, such as a hyperspectral filter (Hypercube™), widefield infrared imagers (S-EOS & GRAND-EOS) and cameras (ZephIR™ 1.7). This gives us a high level of control on the preclinical system, which may be customized to fit customer requirements.

Our standard IR VIVO™ preclinical system offers laser or LED illumination at wavelengths such as 730 nm or 808 nm, which are popular wavelengths for excitation of NIR-II markers such as carbon nanotubes. For detection, we can offer multispectral imaging using a filter wheel and hyperspectral imaging with a continuously tunable spectral range from 850 nm to 1620 nm and a spectral resolution of < 4 nm.

The system is also equipped with a heating plate, gas anesthesia inlet and outlet ports for up to 3 mice. Optional extensions include detection in the visible, which means that one could perform routine experiments carried out by standard preclinical optical imagers in addition to having the capability of doing hyperspectral and NIR-II imaging.

How does imaging in the second biological window differ from other optical imaging wavelengths?

There is reduced scattering as well as minimal absorption and auto-fluorescence by tissue when imaging in the second biological window (1000 to 1700 nm). As a result, there is a much better image contrast, sensitivity and penetration depth into tissue at these wavelengths than traditional visible or infrared optical imaging (i.e. 400-1000 nm).  

Reaching a penetration depth of up to 3 centimeters has a huge impact when imaging small animal like mice, since it allows the visualization of full organs as well as cellular processes in real time with a high spatial resolution.

This positions NIR-II advantageously compared with other small animal imaging modalities. Indeed, MRI, PET and CT imaging can take up minutes to hours to complete a scan, are complex, costly and ionizing in the case of PET and CT.

Furthermore, they cannot provide the micron-scale resolution of NIR-II imaging. Finally, although the increased penetration depth in the second biological window does not allow imaging through the whole human body like MRI, PET or CT, its penetration depth is ideal for applications such as small animal imaging, surgical guidance or tumor resection.

What is available in terms of technology at these wavelengths?

There are many infrared detectors available on the market. For imaging in the second biological window, indium gallium arsenide (InGaAs) based cameras offer the highest sensitivity. Originally restricted to the aerospace and military domain, InGaAs cameras are becoming more and more available to researchers.

Photon Etc. packages its own highly sensitive ZephIR™ 1.7 InGaAs camera operating at -80°C thanks to the integration of a  four-stage TE cooler. This low operating temperature allows signal detection at extremely low noise levels.

As short-wave infrared (SWIR) cameras became more accessible, researchers began testing the potential of working at these wavelengths for life science imaging. They found that a better penetration depth and image clarity could be achieved with this technology, and started developing biomedical markers that could be used at corresponding wavelengths. These fluorescent markers are essential to allow targeting biological entities.

A few NIR-II markers are already commercially available. Although it has been traditionally used for imaging around 800 nm, clinical dye indocyanine green (ICG) turns out to also have a good emission around 1300 nm. There is a clear need for more clinically approved, bright and targetable markers or dyes that emit in the second biological window.

Promising markers which are currently being developed include small molecules, quantum dots, single-walled carbon nanotubes (SWCNT) and rare earth nanoparticles. This growing number of NIR-II markers still falls short compared to the large variety of existing markers for visible imaging.

Photon Etc. works hand in hand with researchers who develop these markers to provide them with imaging tools required for their development.

We offer one of the few microscopes optimized for infrared imaging available thus far on the market, the IMA™. Our microscopes offer the option to do infrared hyperspectral imaging, which allow rapid characterization of the emission wavelength of multiple markers.

Our preclinical NIR-II imager, IR VIVO™, was also developed to fulfill the demand of researchers working in the second biological window.

Caption: Photon etc.’s ZephIR 1.7, SWIR camera

Can you tell us about some of the sample applications of NIR-II Imaging?

NIR-II imaging is ideal for the rapid visualization of deep, small anatomical features with a high degree of clarity. Sample applications include blood flow, lymphatic or metabolic imaging. Tumor detection or cell environment assessment (lipid or microRNA content, pH, temperature, etc.) are other examples which will be discussed shortly.

Diseases related to blood flow such as peripheral arterial disease affect millions of people in America. Mouse models of ischemia are used to develop therapies to improve blood flow recovery. Studies have shown that NIR-II imaging can be used to monitor quantitatively microvascularization-related processes such as tissue perfusion, heart rate or blood flow in small animals.

Indeed, NIR-II allows both visualization of small microvessels at a spatial resolution higher than μCT imaging, and blood flow quantification at a speed matching ultrasound. These capabilities are also relevant for functional imaging of activity states such as muscle motion or brain response to stimuli, which are closely linked to perfusion.

A wide range of NIR-II markers or sensors are being developed to take advantage of the high penetration depth at these wavelengths. Examples include carbon nanotube sensors that allow detection of lipid or microRNA content. Depending on the cellular environment, the emission wavelength of the carbon nanotubes will be shifted and thus allow mapping of the fat content in real time.

It has been shown that changes in a mouse diet reflects lipid content changes. It is expected for this to provide a better insight in the detection and treatment of fat liver disease. In the same way, microRNA content can be assessed through wavelength shifts. In many cases, specific microRNA expression patterns are good disease indicators.  

Source: Galassi, T. V., Jena, P. V., Shah, J., Ao, G., Molitor, E., Bram, Y., … Heller, D. A. (2018). An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo. Science Translational Medicine, 10(461), 1–10. https://doi.org/10.1126/scitranslmed.aar2680

Can the NIR-II imager identify cancer? What impact will this have?

NIR-II imaging can allow cancer detection thanks to intrinsic tissue properties or by using targeted markers. The increased penetration depth and contrast compared with visible imaging could allow superior tumor margin delineation or assessment of tumor volume.

In terms of tumor imaging metrics, it has been shown that using NIR-II markers can yield a significant improvement in tumor-to-normal (T/NT) ratio thanks to reduced background autofluorescence and scattering of tissue at these wavelengths. This means improved ability to detect tumors at earlier stages.

For research purposes, the detection of tumors at earlier stages and the monitoring of their progression may enable a better understanding of tumorigenesis and facilitate the assessment of treatment efficacy. NIR-II also enables monitoring the vascular activity, which is closely related to tumor growth through angiogenesis.

Clinically, NIR-II imaging has the potential to become a highly sensitive, rapid and inexpensive tool for intraoperative image-guided tumor resection. With the appropriate markers developed to target cancer, NIR-II imaging could reduce the incidence of positive surgical margins and therefore the risk of cancer recurrence.

Source: Williams, R. M., Lee, C., Galassi, T. V, Harvey, J. D., Leicher, R., Sirenko, M., … Heller, D. A. (2018). Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant. Science Advances, 4(4). https://doi.org/10.1126/sciadv.aaq1090

What does NIR-II imaging mean for the future of preclinical imaging?

NIR-II imaging will bring an unprecedented combination of fast, high resolution and penetration depth imaging at lower cost and to a broader community than current preclinical imaging techniques.

This will enable to resolve and track single biomedical targets or processes throughout small animals, thereby opening a new window of possibilities for fundamental and biopharmaceutical research.

Where can our readers go to find out more?

Please see our website page for IR VIVO™ system and IMA™.  

Jena, P. V., Roxbury, D., Galassi, T. V., Akkari, L., Horoszko, C. P., Iaea, D. B., … Heller, D. A. (2017). A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux. ACS Nano, 11(11), 10689–10703. https://doi.org/10.1021/acsnano.7b04743

Williams, R. M., Lee, C., Galassi, T. V, Harvey, J. D., Leicher, R., Sirenko, M., … Heller, D. A. (2018). Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant. Science Advances, 4(4). https://doi.org/10.1126/sciadv.aaq1090

About Émilie Beaulieu Ouellet

A biomedical engineer by training, Émilie Beaulieu Ouellet is Application Scientist for life science imaging at Photon Etc. During her graduate studies at Polytechnique Montreal, she specialized in biophotonics, more specifically in the design of microscopes and endoscopes.

Émilie then worked as a biosystems field support specialist and technical representative for microscopy systems at Nikon Instruments. She later joined the Tearney group at Harvard Medical School as an optical engineer for the design and manufacturing of endoscopes for gastrointestinal imaging.

With 10 years experience in biophotonics, plus extensive exposure to varied applications in life science, Émilie strives to bring the latest innovations in biophotonics to the life science market.


REFERENCES

(i) Dion-Bertrand, L.-I. (2016). Hyperspectral Microscopy: A Powerful Technique for Multiplexed Imaging. Biophotonics, 23(8), 20–22.

Antaris, A. L., Chen, H., Cheng, K., Sun, Y., Hong, G., Qu, C., … Dai, H. (2016). A small-molecule dye for NIR-II imaging. Nature Materials, 15(2), 235–242. https://doi.org/10.1038/nmat4476

Ding, F., Zhan, Y., Lu, X., & Sun, Y. (2018). Recent advances in near-infrared II fluorophores for multifunctional biomedical imaging. Chemical Science, 9(19), 4370–4380. https://doi.org/10.1039/c8sc01153b

Bardhan, N. M., Dang, X., Qi, J., & Belcher, A. M. (2018). US 2018/0042483 A1. United States.

Dion-Bertrand, L.-I. (2016). Hyperspectral Microscopy: A Powerful Technique for Multiplexed Imaging. Biophotonics, 23(8), 20–22.

Lessard, Simon & Dion-Bertrand, Laura-Isabelle. (2017). COOLING SWIR SENSORS – AN OVERVIEW. 10.13140/RG.2.2.31365.65764.

Jena, P. V., Roxbury, D., Galassi, T. V., Akkari, L., Horoszko, C. P., Iaea, D. B., … Heller, D. A. (2017). A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux. ACS Nano, 11(11), 10689–10703. https://doi.org/10.1021/acsnano.7b04743

Bruns, O. T., Bischof, T. S., Harris, D. K., Franke, D., Shi, Y., Riedemann, L., … Bawendi, M. G. (2017). Next-generation in vivo optical imaging with short-wave infrared quantum dots. Nature Biomedical Engineering, 1(4). https://doi.org/10.1038/s41551-017-0056

Hong, G., Lee, J. C., Jha, A., Diao, S., Nakayama, K. H., Hou, L., … Huang, N. F. (2014). Near-Infrared II Fluorescence for Imaging Hindlimb Vessel Regeneration with Dynamic Tissue Perfusion Measurement Guosong. Circ Cardiovasc Imaging, 7(3), 517–525. https://doi.org/10.1161/CIRCIMAGING.113.000305

Franke, D., Harris, D. K., Chen, O., Bruns, O. T., Carr, J. A., Wilson, M. W. B., & Bawendi, M. G. (2016). Continuous injection synthesis of indium arsenide quantum dots emissive in the short-wavelength infrared. Nature Communications, 7, 1–9. https://doi.org/10.1038/ncomms12749

Ghosh, D., Bagley, A. F., Na, Y. J., Birrer, M. J., Bhatia, S. N., & Belcher, A. M. (2014). Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes. Proceedings of the National Academy of Sciences, 111(38), 13948–13953. https://doi.org/10.1073/pnas.1400821111

Antaris, A. L., Chen, H., Cheng, K., Sun, Y., Hong, G., Qu, C., … Dai, H. (2016). A small-molecule dye for NIR-II imaging. Nature Materials, 15(2), 235–242. https://doi.org/10.1038/nmat4476

Galassi, T. V., Jena, P. V., Shah, J., Ao, G., Molitor, E., Bram, Y., … Heller, D. A. (2018). An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo. Science Translational Medicine, 10(461), 1–10. https://doi.org/10.1126/scitranslmed.aar2680  

Tagged with:

About author

Related Articles