Mapping the Neurons of the Rat Heart in 3D

An interdisciplinary team of researchers, including MBF Bioscience’s Dr. Susan Tappan and Maci Heal, have created a fully reconstructed, virtual 3D heart, digitally showcasing the heart’s unique network of neurons for the first time. The investigators in this study–appearing May 26 in the journal iScience–created a comprehensive map of the intrinsic cardiac nervous system at a cellular scale using MBF Bioscience’s Tissue Mapper and TissueMaker software. This map also allows for gene expression data to be superimposed within it, which can help determine the functional role that specific neuron clusters play. The researchers say this map will allow neurologists and cardiologists alike to more precisely study the neuroanatomy of the heart and lays the groundwork for developing virtual maps for other major organs.

Achanta, Gorky, Leung, Moss, Robbins, et al., iScience, 2020

This video shows a 3D model in rotation displaying the arrangement of intrinsic cardiac neurons in the rat heart

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Researchers Identify Potential Treatment for Patients at Risk for Alzheimer’s Disease

Neurolucida 360 Used to Analyze Dendrites and Dendritic Spines

Amyloid plaques and tau tangles are the hallmarks of Alzheimer’s disease (AD) pathology, but synapse loss is what causes cognitive decline, scientists say. In a paper published in Science Signaling, researchers at the Herskowitz Lab, at the University of Alabama at Birmingham, used Neurolucida 360 to analyze spine density and dendritic length in hAPP mice — a mouse model of AD. Their findings describe a treatment that could protect against synapse loss and prevent the onset of dementia in patients at risk for Alzheimer’s disease.

Targeting LIMK1 to Protect Against Dendritic Damage

In their study, the scientists targeted LIMK1, an enzyme that regulates the size and density of dendritic spines. Previous studies have shown that in animal models of AD, LIMK1 activity is increased, causing synaptic hyperactivity and dendritic damage. After confirming this phenomenon, the research team set out to find a way to inhibit LIMK1, which lies downstream of two other important players in dementia pathology — the Rho-associated kinases known as ROCK1 and ROCK2.

Representative maximum-intensity high-resolution confocal microscope images of dye-filled dendrites, from CA1 hippocampal neurons in mice, after deconvolution and corresponding 3D digital reconstruction models of dendrites. Scale bar, 5 μm. Colors in digital reconstructions correspond to dendritic protrusion classes: blue, thin spines; orange, stubby spines; green, mushroom spines; and yellow, dendritic filopodia.

 

Previous studies have shown that severe side effects including fatally low blood pressure are associated with the inhibition of ROCK1 and ROCK2, so the researchers looked further down the signaling pathway to the LIMK1 point, potentially discovering a truly valid target in the fight to prevent dementia onset.

Since LIMK1 has also been a target in cancer treatment, the researchers turned to SR7826, an experimental drug currently in development to treat cancer patients. They found that administering SR7826 suppressed LIMK1 activity and protected dendritic morphology against the damage commonly seen in a brain afflicted with dementia. By reconstructing the mouse neurons with Neurolucida 360, they observed increased dendritic spine length and density in the experimental group, compared to controls.

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MBF Bioscience Secures Exclusive License from Columbia University to Create New Light-Sheet Microscope System

For Immediate Release:

Williston, VT (February 04, 2020) — MBF Bioscience’s revolutionary light sheet microscope system, ClearScope, sets a new standard for microscopic imaging.

The new decade is poised to bring about incredible scientific innovations, and MBF Bioscience is leading the charge in 2020 with the creation of the “light sheet theta microscope” system, ClearScope.

MBF Bioscience secured exclusive license from Columbia University to develop the light sheet theta microscope technology invented by Dr. Raju Tomer. This patent-pending technology in ClearScope leap frogs a number of inherent limitations of other light sheet microscopes. ClearScope will be commercially released this year.

ClearScope performs high-resolution, 3D imaging of intact, cleared specimens that are larger than any other light sheet microscope is capable of imaging. The technology permits fast imaging speed, high- quality imaging and low photo-bleaching. With the exclusive dual, oblique light sheets providing homogeneous illumination, MBF Bioscience has created a microscope system superior to all existing commercial light sheet microscopes. It is compatible with tissue clearing techniques including CLARITY, uDISCO, SeeDB, Scale and Binaree.

President and co-founder of MBF Bioscience, Jack Glaser says, “Dr. Tomer’s, revolutionary design of light sheet theta microscopy, and the new capabilities it provides, will have a dramatic impact in scientific research. We are excited to bring this technology to market in ClearScope. ”

Dr. Raju Tomer, assistant professor of biological sciences at Columbia University says, “I am very excited about the licensing of our light sheet theta microscope technology to MBF Bioscience for developing a robust and user-friendly ClearScope product. This technology has clear potential to revolutionize high-resolution, quantitative imaging of very large cleared samples. It will also be a valuable instrument for dynamic imaging of live specimens. I think MBF Bioscience, with its extensive expertise in neuroscience imaging and data analytics, is a natural partner to take it beyond a lab instrument stage, to benefit the scientific community at large.”

With the ability to image cleared tissue of virtually any XY size, ClearScope has the ability to completely revolutionize the way researchers image and collect data of tissue specimens. ClearScope image data can be analyzed with MBF’s flagship software solutions, Neurolucida 360, Vesselucida 360 and Stereo Investigator.

To learn more about ClearScope visit: www.mbfbioscience.com/clearscope

About MBF Bioscience: MBF Bioscience integrates the world’s leading microscope systems with our revolutionary quantitative imaging and visualization software to accelerate research in the fields of: stereology, neuron and microvasculature reconstruction, vascular analysis, worm tracking, brain mapping and big image data management in medical research and education.

Since 1988, MBF Bioscience has forged a rich history of creating innovative products to empower biological researchers with the quantitative analysis tools they need to obtain accurate, unbiased results. With offices in North America, Europe, Japan, and China, MBF Bioscience has helped researchers across the globe publish over 15,000 peer-reviewed papers in peer reviewed journals. MBF Bioscience partners with the NIH and distinguished scientists across the world to continue their commitment to neuroscience research with their software technology, and also in the fields of stem cells, pulmonology, oncology, and toxicology. For more information visit www.mbfbioscience.com or follow MBF Bioscience on Facebook, Twitter, and LinkedIn, or compete in our image contest at www.neuroart.com

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Media Contact:
Pasang Sherpa
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MBF Bioscience Announces Launch of MicroDynamix

New Software Application Quantifies Changes in Dendritic Spine Morphology Over Time

Williston, VT — December 10, 2019 — The ability to track the changes that occur in dendritic spine morphology over time is critical to many scientific studies, which is why MBF Bioscience is pleased to announce the launch of MicroDynamix. This powerful new software application helps neuroscientists acquire more information about morphological changes in the brain with impressive speed. MicroDynamix also offers the ability to visualize and quantify dendritic spine morphology over time.

After loading image data acquired at different time points from in vivo and in vitro imaging sessions, MicroDynamix automatically aligns the images in 3D, then reconstructs dendritic branches, detects dendritic spines, and identifies important metrics — such as length, thickness, and overall number, for accurate quantitative comparison.

Since all images are managed within a single framework, the research process is streamlined, saving neuroscientists time in the laboratory that would otherwise be spent locating and manually finding the same spine. MicroDynamix also offers researchers the ability to view two 3D images side-by-side — an invaluable feature for tracking the changes that occur in dendritic spine morphology over time.

Over the course of an experiment, researchers have the ability to upload new images and compare the same region at different time points with MicroDynamix thanks to the software’s sophisticated algorithms. Dendrites and spines are automatically associated across images, so that the same dendrite imaged at any timepoint — two days later, two weeks later, or two months later is automatically detected and identified. The researcher is then able to very clearly view and quantify the changes in morphology that may or may not have occurred.

The software also includes customizable graphs, which give researchers the ability to present their data visually. Key metrics, such as the number and density of spines per time point; head diameter, plane angle, and luminance of individual spines; as well as the total number of spines within a specific region can all be clearly presented in tabular and graph form.

“MicroDynamix provides researchers with the unprecedented capability to get more information about changes in dendritic spines observed in repeated imaging experiments,” says MBF Bioscience President Jack Glaser. “We’re so pleased to announce the launch of this powerful new product for visualizing and quantifying spine morphology over time.”

To learn more about MicroDynamix visit https://www.mbfbioscience.com/microdynamix 

About MBF Bioscience: MBF Bioscience creates quantitative imaging and visualization software for stereology, neuron reconstruction, vascular analysis, c. elegans behavior analysis and medical education, integrated with the world’s leading microscope systems, to empower research.

Our development team and staff scientists are actively engaged with leading bioscience researchers, constantly working to refine our products based on state-of-the-art scientific advances in the field.

Founded as MicroBrightField, Inc. in 1988, we changed our name to MBF Bioscience in 2005 to reflect the expansion of our products and services to new microscopy techniques in all fields of biological research and education. While we continue to specialize in neuroscience research, our products are also used extensively in the research fields of stem cells, lung, kidney, cardiac, cancer, and toxicology.

MBF Bioscience has grown into a global business, with offices in North America, Europe, Japan, and China, and a dealer network active on five continents. Our commitment to innovative products and unrivaled customer support has gained high praise from distinguished scientists who use our products all over the world. Our flagship products Stereo Investigator and Neurolucida are the most widely-used analysis systems for stereology and neuron reconstruction.

For more information visit www.mbfbioscience.com or follow MBF Bioscience on Facebook, Twitter, and LinkedIn, and track our NeuroArt.com contest on Instagram.

 

Better. Faster. More Efficient than Ever Before.

Something big is happening at MBF Bioscience. Something that will make your work better than ever before.

Over the past 32 years we have taken pride in offering our customers the best tools for their research. And we are constantly striving to make things even better for you.

Get ready, because something extraordinary is coming in 2020. Something that will make your work faster and more efficient. Something that can handle big files and analyze them with stunning speed and precision. We are beyond excited to share our big news with you.

Watch this space in 2020 to learn more.

A GPS for the brain and so much more

Scientists use NeuroInfo to help navigate the brain and compare findings across labs

Reproducibility has always been a primary goal in science. But the human effort involved in replicating a research study and analyzing the results, can be considerable. NeuroInfo® is a revolutionary new tool that scientists are using to register whole slide images into a standardized mouse brain atlas in an easy, automated way. Images and subsequent measurements can then be cross-referenced against findings from a myriad of other studies.

NeuroInfo

Coronal mouse brain section from the Laboratory of Systems Neuroscience of Dr. Charles Gerfen, NIMH Bethesda, Maryland

Meeting the demands of users is always a priority for MBF Bioscience, and working with customers like Dr. Charles Gerfen of the National Institute of Mental Health provided a major impetus for developing NeuroInfo into such a revolutionary product.

“The major advance,” said Dr. Gerfen, “is that we’re able to analyze projections from within and between different areas of the cerebral cortex to determine organizational principles of the cerebral cortex,” Along with Dr. Bryan M. Hooks of the University of Pittsburgh School of Medicine, Dr. Gerfen uses NeuroInfo to trace pyramidal neuron projections in Cre-driver mice (Hooks, et al 2018).

As outlined in a study published in Nature Communications, the research team first used MBF Bioscience’s BrainMaker functionality of NeuroInfo to reconstruct four Cre-recombinase driver mouse brains with sections imaged with Neurolucida. They then registered the reconstructed brains into the Allen Mouse Brain Atlas and then collectively visualized experimental data overlain with the atlas to determine exactly how the four populations of cortical pyramidal neurons they were tracking fit within the greater structure of the brain. “Essentially every pixel or image in our original images could be assigned to one of the 2500 brain structures in the Allen Atlas, said Dr. Gerfen.

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In Memoriam: Edmund M. Glaser, PhD

Dr. Edmund Glaser devoted his career of more than four decades to the field of neuroscience. Most notably, in 1963, he co-invented computer microscopy, a pioneering method of quantifying the brain’s morphometry. This technology, for the first time, applied computer techniques to the neuroanatomical world, permitting scientists to precisely quantify the brain’s three-dimensional structure. It simplified time-consuming, inexact classical methodologies in an efficient and cost-effective method. By 1995, the year of Dr. Glaser’s retirement, computer microscopy had been adopted by thousands of neuroscience laboratories throughout the world.

Dr.Edmund GlaserDr. Glaser started his college education in his hometown, New York City, studying Electrical Engineering at The Cooper Union. In the midst of his college career, he was drafted and served in the U.S. Army during WWII. His duty took him to Nuremberg, where he was a sound recordist and photographer who documented the Medical War Trials of infamous Nazi physicians. After his military service, he completed his bachelor’s degree in 1949. After doing early project work in communications systems and guided missiles for the U.S. Air Force, he soon became attracted to the emerging fields of computing, information theory, and artificial intelligence. In 1952, he returned to his academic studies in engineering. He received a PhD from Johns Hopkins University in 1960 and then secured a postdoctoral fellowship in its Department of Physiology in the School of Medicine.

In 1963, Dr. Glaser teamed up with Dr. Hendrik Van der Loos, a neuroanatomist at Johns Hopkins, to study the complex morphology of the brain’s cerebral cortex. They encountered the shortcomings of the time’s tedious neuroanatomical techniques and noted the need to revamp the prevailing methods of analyzing neuron morphology and neuronal networks within the cerebral cortex. It was then that they formulated the design and the construction of the first computer microscope.

Computer microscopy at that time was based on the use of analog computer technology. Glaser and Van der Loos demonstrated the great improvements that could made in neuroanatomy by adapting computer technology, it showed the practical way to represent the brain’s structure in its intrinsic three-dimensional reality. In so doing, the quantification of neuroanatomy was wholly revolutionized. Tracing neuronal structures was reduced from hours to minutes and measurement precision was able to achieve fractional micron accuracy. What is more, large assemblies of neuronal networks could be examined in quantitative detail in three dimensions.

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Scientists use Vesselucida 360 to quantify brain vasculature in mTBI model

It is not uncommon for war veterans returning home from war-zones like Iraq and Afghanistan to suffer from blast-induced traumatic brain injuries (TBI). In these situations, the most common types of blasts are lower level blasts, the kind that produce mild TBIs (mTBI). Though the effects of a mTBI aren’t visible from the outside, scientists say the blood vessels inside the brain are deeply altered.

In their study of a mouse model of mTBI that mimics the blast exposure associated with human mild TBI, a research team, that includes MBF Bioscience Scientific Director Dr. Susan Tappan, say that low-level blast exposure disrupts the way cells interact with each other within the brain’s neurovascular unit.

Fig:1 Chronic vascular pathology in blast-exposed rats revealed by micro-CT scanning. Two control and two blast-exposed rats were transcardially perfused with the Brite Vu contrast agent at 10 months after blast exposure. Brains were scanned at a resolution of 7.5 μm using equispaced angles of view around 360°, and 3D reconstructions were prepared with Bruker’s CTVox 3D visualization software. a-d MIP images of volume-rendered brain vasculature from two control (a, b) and two blast-exposed (c, d) rats revealed diffuse thinning of the brain vasculature in the blast-exposed rats. Scale bar, 2 mm. e-h Trace sagittal reconstructions used for the automated quantitation from control (e-f) and blastexposed rats (g-h) o-p Higher magnification views of the regions outlined by the boxes in panels (f) and (h). Scale bars, 1 mm for (e-h), and 0.6mm for (o-p). i-n Reconstructions of coronal optical sections from the brains of control (i, k) and blast-exposed (j, l) animals. Panels (i) and (j) correspond approximately to coordinates interaural 12.24–9.48 mm and panels (k) and (l) correspond approximately to coordinates interaural 6.94–3.24 mm. Lateral views of (i) and (j) are shown in (m) and (n), respectively. Vessels were color coded to allow visualization of individual vessels automatically traced by the Vesselucida 360 software. Note the general loss of radial organization in the blast-exposed shown in panel (j). Scale bar, 1 mm for (i-n)

Aiming to mimic an event often experienced by soldiers and military personnel in war-torn regions, the scientists exposed rats to a series of three blasts — one blast per day, over three consecutive days. Though the rats developed behaviors typical to chronic PTSD, their neuronal pathology, at least at the light and electron microscopy levels remained unchanged, according to the study. However, when the researchers examined the rat brains on a vascular level, they found evidence of chronic damage.

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MBF Bioscience research team contributes novel dendritic spine analysis in study published in Science

Combination of new microscopy and expansion tissue preparation methods facilitate better and faster analysis of subcellular neural elements.

Today, the journal Science published a paper authored by a research team led by Dr. Ed Boyden of MIT and Nobel Prize recipient Dr. Eric Betzig of Janelia Research Campus. Among the authors are MBF Bioscience Scientific Director Dr. Susan Tappan and Senior Software Engineer Alfredo Rodriguez. In the paper, the researchers introduce new analyses for neural circuits at nanoscale resolutions.

Combining microscopy methods that create high resolution 3D images from whole brains and tissue that have been made physically larger, the researchers imaged a mouse cortex and fruit fly brain in their study “Cortical column and whole-brain imaging of neural circuits with molecular contrast and nanoscale resolution (Gao et al, 2019).”

By creating enhanced processing and analysis tools in MBF Bioscience’s Stereo Investigator and Neurolucida 360 software, Dr. Tappan and Mr. Rodriguez analyzed these images to obtain comprehensive morphometrics of delicate dendritic spines at a greater accuracy than ever before.

GAO ET AL./SCIENCE 2019

“We combined expansion microscopy and lattice light sheet microscopy (ExLLSM) to image the nanoscale spatial relationships between proteins across the thickness of the mouse cortex or the entire Drosophila brain, including synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly neuropil domain.” (Gao et al, 2019)

While several forms of microscopy exist that have the ability to image subcellular neural elements, scientists say that each of these methods is lacking in one way or another. According to the paper, the combination of expansion microscopy with lattice-light sheet microscopy gives the most effective results, while considerably decreasing the time spent carrying out the experiment.

“I believe this type of imaging represents a major milestone in terms of the accuracy that can be achieved in dendritic spine morphometry from light microscopy,” Mr. Rodriguez said.

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MBF Bioscience receives NIH funding to support innovative research program on the peripheral nervous system

FOR IMMEDIATE RELEASE

MBF Bioscience Williston, VT – January 9, 2019 – MBF Bioscience is pleased to announce our participation in the Stimulating Peripheral Activity to Relieve Conditions (SPARC) program. Funded by the National Institutes of Health (NIH), this extensive research initiative is a vast collaborative effort, which aims to deepen the understanding of how the peripheral nervous system impacts internal organ function.

“We are honored to be working in collaboration with over 40 research teams in the United States and around the world who are making revolutionary discoveries about how the network of nerves located outside the brain and spinal cord affect organs such as the heart, stomach, and bladder, and what role these nerves play in diseases like hypertension and type II diabetes as well as gastrointestinal and inflammatory disorders,” says Jack Glaser, President of MBF Bioscience.

To facilitate this important research, MBF Bioscience will provide the collaborating research scientists with both software and support. Specifically, we will provide image segmentation tools developed to handle large and diverse amounts of scientific image data. Software applications such as Neurolucida 360®, Tissue Mapper™ and Tissue Maker™ will enable researchers to image and analyze nerves, tissues, and entire organs in 2D and 3D.

“Representing the innervation patterns accurately and robustly is an essential contribution to the generation of representative models that can be used for simulations.  We are working with our partners at the University of Auckland, under the direction of Professor Peter Hunter, to create these models for each organ system that will be an enduring resource for scientists for years to come,” says Susan Tappan, Scientific Director at MBF Bioscience.

Researchers involved in the SPARC program are making important advances in health and medicine, which may lead to the development of new therapies for managing an array of illnesses and disorders. Some examples of research areas include subcutaneous nerve stimulation for arrhythmia control, sensory neuromodulation of the esophagus, and mapping of the neural circuitry of bone marrow. We are thrilled about this opportunity to work in partnership with such an impressive array of research teams on this ground-breaking project.

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