Frequently Asked Questions

The list of Frequently Asked Questions has been organized into categories for Cell Sense, V-Sense, and general information about Celsense. Please click a category below to view the questions and answers for that category.

If your question is not found in the answers below, please send your question to info@celsense.com.

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  • Cell Sense
  • V-Sense

Why track cells?

In the context of cell therapy, the trafficking of cells (the pharmacokinetics of the cellular composition or PK), is fundamental to proving the investigator’s hypotheses for mechanism of action and safety. PK data includes the initial delivery of the therapy, its migration, its persistence and/or clearance. The hypothesis for mechanism of action should include the site of action, a min/max dose at the site of action, and the min/max duration at the site of action. The hypothesis for safety should include a clearance pathway for dead cells, and a maximum dose for off target delivery to sites with high risk causing undesirable side effects.

What is MRI?

Magnetic Resonance Imaging (MRI) is a commonly used medical imaging technology used to visualize body tissues in 3D. The technique involves placing the patient or subject in a magnetic field which causes the hydrogen atoms in water to align along a single axis, perturbing the aligned hydrogen atoms with a radio signal, and then receiving a radio signal given off by the atoms as they move back to an aligned position. Using a powerful software, the received radio signal is converted into a richly detailed 3-dimensional picture of the tissues of the patient.

Is MRI safe?

Each year, millions of patients around the world have an MRI procedure without any dangerous side effects. MRI is commonly used to diagnose and stage the progress of many diseases. At worst, some patients complain about the loud hum of the magnet and/or the tight quarters inside the narrow tube used to contain the magnetic field. Unlike X-Ray, CAT scans, and PET scans, there is no ionizing radiation with MRI. Hence, there are no limits on MRI procedures per year or per lifetime.

What is Cell Sense?

Cell Sense is a proprietary MRI tracer agent comprised of a perfluorocarbon emulsion used to label living mammalian cells in culture. When the living cells are administered to a patient or a test subject, the tracer agent renders the labeled cell detectable in fluorine MRI.

Why Fluorine MRI?

Fluorine atoms are also detectable by MRI, they just detected at a lower radio frequency than the hydrogen in water. Since fluorine is not typically found in the human body, it has high specificity versus any background signal. It is sometimes called “hot spot” imaging. Also, fluorocarbon molecules appear to be inert in biology. They do not chemically react with any substances in cells, tissues and organisms. The perfluorocarbon molecules used to make Celsense product have a long history for use in man as artificial blood substitutes. Hence, their safety and clearance pathways are well studied and known to drug regulators.

What is Voxel Tracker?

Voxel Tracker is an interactive software suite offered by Celsense to maximize the value of the fluorine MRI data set. Available to customers for free, the software permits investigators to:

  • Upload and store imaging data sets in a cloud environment
  • Display the Cell Sense labeled cells in their anatomical context by merging the hydrogen and fluorine image data sets
  • Compute the number of Cell Sense labeled cells in a user-defined region of interest (ROI)
  • Develop statistics for the accuracy of the number of Cell Sense labeled cells in an ROI based on noise in the MRI image

How do I get access to Voxel Tracker?

Send an email with your name and affiliation to info@celsense.com, and we will send you credentials to access the system. There is a tutorial and a comprehensive manual available online.

Is Fluorine MRI complicated?

Most MRI scanners, clinical and preclinical, are designed and built to image different chemical nuclei. This is sometimes referred to a multi-nuclear spectroscopy. To avoid potential mistakes, many clinical MRI scanners have this feature disabled. The workflow is fairly straightforward. Both a hydrogen and fluorine image are acquired during the imaging session. In many cases, this can be pre-programmed into the imaging equipment before the patient arrives. In some cases, the imaging technician must set the scanner up in real time. After the images acquired, they are merged to show the Cell Sense labeled cells in their anatomical context. The company’s software tool Voxel Tracker can help with this post-processing step.

How do I label my cells with Cell Sense?

Cell Sense is added to the media of cells in culture and left in the media for a period of time while the cells take up the emulsion droplets. The amount of Cell Sense added to the media (concentration) and the incubation period (duration) varies based on the tissue culture conditions, cell type, and other constraints imposed by manufacturing protocols. Typically, investigators conduce a few simple in vitro experiments varying concentration and duration to optimize the labeling protocol.

Are transfection agents required?

Cell Sense has been engineered to be taken up by cells in culture without the use of transfection agents. The Cell Sense emulsion droplets have a diameter of approximately 165 nanometers and have been engineered to have a slightly negative charge. This combination of size and charge promotes cellular uptake by endocytosis. It has been shown that most cell types take up the tracer agent in any low serum tissue culture condition.

How long do cells retain the Cell Sense label?

Experimental data demonstrates that viable cells permanently retain the Cell Sense label.

How much Cell Sense do cells take up?

The amount of Cell Sense per cell is described as fluorine atoms per cell (19F/cell) and is dependent on cell type and the absolute size of the cell. 19F/cell is typically measured in a lysed pellet of cells by high resolution nuclear magnetic resonance (NMR). Typically, small cells such as human T cells and NK cells take up around 5X1011 19F/cell, and larger cells such as human dendritic cells take up around 5X1013 19F/cell.

What are the limits of detection for Cell Sense?

There isn’t a simple answer to this often asked question. MRI is not affected by tissue type or tissue depth, but it does have well characterized limits of detection. In cell tracking, we typically describe the limit of detection as the minimum number of cells that can be detected in a 3 dimensional shape called a volume element or voxel. The size of the voxel is arbitrarily set by the investigator, and might be as small as sub-millimeter or as large as an entire organ (the tip of a lymph node versus the entire liver). The limit of detection per voxel is a function the magnet strength MRI scanner, the geometry of the MRI coil, MRI scanner settings, and most importantly, the amount of 19F/cell. The academic literature indicates a range from 5,000 large cells in a high field preclinical scanner to 150,000 small cells in a high field clinical scanner.

What is the clearance pathway for Cell Sense?

The clearance pathway for Cell Sense is tied to the fate of the cells administered to a patient or subject. Cell Sense labeled cells that die and disintegrate (lysis), release the tracer agent into the surrounding tissues. The experimental data indicates that the label is rapidly cleared through the reticuloendothelial systems (RES) to Kupffer cells in the liver. In the liver, the tracer agent is slowly released back into the blood and exhaled. Theoretically, labeled dead cells may be taken up by macrophage, and persist in tissues. Sometimes referred to as “bystander cells”, this phenomena would render a “false positive” in MRI.

How does quantification work?

Of keen interest to most investigators is the number of Cell Sense labeled cells in a region of interest (ROI). This in known as quantification, and fluorine MRI is particularly amenable to counting the number of cells in an ROI. Typically, the amount of 19F/cell is measured using NMR prior to administering the cell product to a patient or subject. During the imaging session, an MRI reference is placed in the field of view in the MRI image. The MRI reference contains a fluorine sample with a known number of fluorine atoms. After this image is completed, the imaging intensity of the fluorine reference is compared to the imaging intensity of labeled cells in the ROI. The relative intensity can be used to accurately calculate the number of cells in the ROI. The company’s Voxel Tracker software makes this process easy, and also takes into account the noise in the MRI data.

What happens when cells divide?

Cell Sense labeled cells contain thousands of perfluorocarbon emulsion droplets. These droplets are disbursed throughout the cytoplasm, typically in low pH compartments. When a cell divides (mitosis), the droplets appear to be evenly distributed between the daughter cells. With the passage of time, the dilution of the Cell Sense label will reduce the accuracy of quantification and will affect the limits of detection. The good news is that most studies confirm that Cell Sense does not interfere with either proliferation rates or differentiation pathways.

Can I use Cell Sense in a clinical trial?

Yes. Cell Sense can be used in preclinical studies, but it was developed for clinical use. To use Cell Sense in an authorized study, drug regulators typically require an in vitro data set comparing the phenotype and function of the Cell Sense labeled cells to unlabeled cells. The tests should include data that verifies that Cell Sense labeled cells meet the study sponsor’s release criteria for the cell therapy product. In the US and Canada, drug regulators will also require the study sponsor to cross reference the Drug Master File for Cell Sense.

Should I use a Dual Mode version of Cell Sense?

The Cell Sense product family includes reagents where a bright fluorescent dye is conjugated to the fluorocarbon. Our stock versions of Dual Mode Cell Sense include a FITC Green and a Texas Red. These versions are typically used for two types of studies: to measure the homogeneity of cell labeling using flow cytometry, and to confirm the MRI data using histopathology in preclinical experiments. The Dual Mode versions of Cell Sense are not authorized for use in clinical studies.

Can I use Cell Sense to track small molecules?

No. Small molecules and proteins can by conjugated to fluorocarbons, but MRI is not sufficiently sensitive to detect small quantities of fluorine in the body.

What are the storage conditions and shelf life for Cell Sense?

  • Although the Cell Sense reagents are stable at room temperature, we recommend storage at 5° C. DO NOT FREEZE.
  • The shelf life for unopened vials is 12 months after the date of manufacture (which is printed on the vial label).
  • The shelf life for opened vials is 2 weeks after opening.

How do place an order for Cell Sense?

Contact the company at info@celsense.com. Most Cell Sense reagents are carried as stock items and are usually available for prompt delivery. All reagent products are shipped by FedEx overnight.

Where are the Celsense reagents manufactured?

All of the Celsense reagents are manufactured at our headquarters location in Pittsburgh, Pennsylvania, USA.

Is Celsense owned by another company?

No. The company’s stock is owned by a group of individual investors. The investors are represented by a distinguished Board of Directors, several of whom were founders of the company.

Do any distributors carry Celsense reagents?

Not as a regular stock item. From time to time, distributors as act as intermediaries for the convenience of customers.

Why image inflammation?

In the context of therapeutic development, visualizing changes in site specific inflammation over time can unlock data regarding immune response to an intervention. In many models of disease, existing methods to measure changes in immune response are limited in scope (discernable changes in morphology) and/or difficult to quantitate due to sampling (histological examination of tissues). Imaging can be non-invasive and easily repeated over time.

What is MRI?

Magnetic Resonance Imaging (MRI) is a commonly used medical imaging technology used to visualize body tissues in 3D. The technique involves placing the patient or subject in a magnetic field which causes the hydrogen atoms in water to align along a single axis, perturbing the aligned hydrogen atoms with a radio signal, and then receiving a radio signal given off by the atoms as they move back to an aligned position. Using a powerful software, the received radio signal is converted into a richly detailed 3-dimensional picture of the tissues of the patient.

Is MRI safe?

Each year, millions of patients around the world have an MRI procedure without any dangerous side effects. MRI is commonly used to diagnose and stage the progress of many diseases. At worst, some patients complain about the loud hum of the magnet and/or the tight quarters inside the narrow tube used to contain the magnetic field. Unlike X-Ray, CAT scans, and PET scans, there is no ionizing radiation with MRI. Hence, there are no limits on MRI procedures per year or per lifetime.

What is V-Sense?

V-Sense is a proprietary MRI tracer agent comprised of a perfluorocarbon emulsion that is used to visualize inflammation in preclinical studies. V-Sense is formulated for IV injection and a long half life in blood. Emulsion droplets are taken up by resident leukocytes (macrophage, monocytes, and neutrophils), rendering them detectable in fluorine MRI. Leukocytes that are participating in an inflammatory response create hot spots detectable in MRI data set. The amount of fluorine in a region of interest is directly proportional to the number of inflammatory cells present.

Why Fluorine MRI?

Fluorine atoms are also detectable by MRI, they just detected at a lower radio frequency than the hydrogen in water. Since fluorine is not typically found in the human body, it has high specificity versus any background signal. It is sometimes called “hot spot” imaging. Also, fluorocarbon molecules appear to be inert in biology. They do not chemically react with any substances in cells, tissues and organisms. The perfluorocarbon molecules used to make Celsense product have a long history for use in man as artificial blood substitutes. Hence, their safety and clearance pathways are well studied and known to drug regulators.

What is Voxel Tracker?

Voxel Tracker is an interactive software suite offered by Celsense to maximize the value of the fluorine MRI data set. Available to customers for free, the software permits investigators to:

  • Upload and store imaging data sets in a cloud environment
  • Display the Cell Sense labeled cells in their anatomical context by merging the hydrogen and fluorine image data sets
  • Compute the number of Cell Sense labeled cells in a user-defined region of interest (ROI)
  • Develop statistics for the accuracy of the number of Cell Sense labeled cells in an ROI based on noise in the MRI image

How do I get access to Voxel Tracker?

Send an email with your name and affiliation to info@celsense.com, and we will send you credentials to access the system. There is a tutorial and a comprehensive manual available online.

Is Fluorine MRI complicated?

Most MRI scanners, clinical and preclinical, are designed and built to image different chemical nuclei. This is sometimes referred to a multi-nuclear spectroscopy. To avoid potential mistakes, many clinical MRI scanners have this feature disabled. The workflow is fairly straightforward. Both a hydrogen and fluorine image are acquired during the imaging session. In many cases, this can be pre-programmed into the imaging equipment before the patient arrives. In some cases, the imaging technician must set the scanner up in real time. After the images acquired, they are merged to show the Cell Sense labeled cells in their anatomical context. The company’s software tool Voxel Tracker can help with this post-processing step.

What is the work flow for V-Sense?

In a typical model of disease or injury, V-Sense is injected IV about 24 hours prior to the desired measurement point. For rodents, the dose given should be between 7.5% and 10% of the test subject’s blood volume. The reagent should be injected “slowly” to allow the subject to adjust to the change in blood volume. After 24 hours, the subject is placed in an MRI scanner, and the conventional hydrogen and fluorine images are acquired. When the scans are complete, the to image data sets are combined to show the inflammation in its anatomical context. The subjects can be imaged at subsequent time periods to measure changes in the leukocyte burden in a region of interest.

How long do cells retain the V-Sense label?

Experimental data demonstrates that viable leukocytes permanently retain the V-Sense label. Since these are typically short lived cells, the fluorine signal will decline over time as leukocytes die and are cleared via the reticuloendothelial system (RES).

What is the clearance pathway for V-Sense?

The clearance pathway for V-Sense is the reticuloendothelial system (RES). For subjects with a healthy liver, much of the V-Sense injected is taken up by Kupffer cells in the liver. V-Sense labeled leukocytes eventually die and disintegrate (lysis), releasing the tracer agent into the surrounding tissues. The experimental data indicates that the label is rapidly cleared through the RES. In the liver, the tracer agent is slowly released back into the blood and exhaled. Theoretically, labeled dead leukocytes may be taken up by other leukocytes, and persist in tissues. This phenomena has never been definitively detected or measured.

How does quantification work?

Of keen interest to most investigators is changes in the leukocyte burden in a region of interest (ROI). Unlike Cell Sense, where the amount of 19F/cell is measured using NMR prior to administering the cell product to a patient or subject, we can only measure the amount of fluorine in the ROI. Prior studied indicate the amount of fluorine is directly proportional to the number of leukocytes in the ROI. The amount of fluorine signal is sometimes referred to as the Inflammation Index. The company’s Voxel Tracker software makes this process easy, and also takes into account the noise in the MRI data.

Can I use V-Sense in a clinical study?

No. V-Sense can only be used in preclinical studies.

Should I use a Dual Mode version of V-Sense?

The V-Sense product family includes reagents where a bright fluorescent dye is conjugated to the reagent. Our stock versions of Dual Mode V-Sense include a FITC Green, a Texas Red and a Cy-7 NIR dye. These versions are typically used to confirm the MRI data using histopathology in preclinical experiments.

What are the storage conditions and shelf life for V-Sense?

  • Although the V-Sense reagents are stable at room temperature, we recommend storage at 5° C. DO NOT FREEZE.
  • The shelf life for unopened vials is 12 months after the date of manufacture (which is printed on the vial label).
  • The shelf life for opened vials is 2 weeks after opening.

How do place an order for V-Sense?

Contact the company at info@celsense.com. Most V-Sense reagents are carried as stock items and are available for prompt delivery. All reagent products are shipped by FedEx overnight.

Where are the Celsense reagents manufactured?

All of the Celsense reagents are manufactured at our headquarters location in Pittsburgh, Pennsylvania, USA.

Is Celsense owned by another company?

No. The company’s stock is owned by a group of individual investors. The investors are represented by a distinguished Board of Directors, several of whom were founders of the company.

Do any distributors carry Celsense reagents?

Not as a regular stock item. From time to time, distributors as act as intermediaries for the convenience of customers.

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