Posts Tagged ‘Cognitive Science/Neuroscience’

Despite heated discussion over whether it works, the FDA has approved Aduhelm, bringing a new ray of hope to the Alzheimer’s patients.

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

On Monday, 7th June 2021, a controversial new Alzheimer’s Disease treatment was licensed in the United States for the first time in nearly 20 years, sparking calls for it to be made available worldwide despite conflicting evidence about its usefulness. The drug was designed for people with mild cognitive impairment, not severe dementia, and it was designed to delay the progression of Alzheimer’s disease rather than only alleviate symptoms.


The Controversies

The route to FDA clearance for Aducanumab has been bumpy – and contentious.

Though doctors, patients, and the organizations that assist them are in desperate need of therapies that can delay mental decline, scientists question the efficacy of the new medicine, Aducanumab or Aduhelm. In March 2019, two trials were halted because the medications looked to be ineffective. “The futility analysis revealed that the studies were most likely to fail,” said Isaacson of Weill Cornell Medicine and NewYork-Presbyterian. Biogen, the drug’s manufacturer revealed several months later that a fresh analysis with more participants found that individuals who got high doses of Aducanumab exhibited a reduction in clinical decline in one experiment. Patients treated with high-dose Aducanumab had 22% reduced clinical impairment in their cognitive health at 18 months, indicating that the advancement of their early Alzheimer’s disease was halted, according to FDA briefing documents from last year.

When the FDA’s members were split on the merits of the application in November, it was rejected. Three of its advisers went public, claiming that there was insufficient evidence that it worked in a scientific journal. They were concerned that if the medicine was approved, it might reduce the threshold for future approvals, owing to the scarcity of Alzheimer’s treatments.

Dr. Caleb Alexander, a drug safety and effectiveness expert at the Johns Hopkins Bloomberg School of Public Health, was one of the FDA advisers who was concerned that the data presented to the agency was a reanalysis after the experiment was stopped. It was “like the Texas sharpshooter fallacy,” he told the New York Times, “where the sharpshooter blows up a barn and then goes and paints a bullseye around the cluster of holes he loves.”

Some organizations, such as the non-profit Public Citizen’s Health Research Group, claimed that the FDA should not approve Aducanumab for the treatment of Alzheimer’s disease because there is insufficient proof of its efficacy.

The drug is a monoclonal antibody that inhibits the formation of amyloid protein plaques in the brain, which are thought to be the cause of Alzheimer’s disease. The majority of Alzheimer’s medications have attempted to erase these plaques.

Aducanumab appears to do this in some patients, but only when the disease is in its early stages. This means that people must be checked to see if they have the disease. Many persons with memory loss are hesitant to undergo testing because there is now no treatment available.

The few Alzheimer’s medications available appear to have limited effectiveness. When Aricept, also known as Donepezil, was approved more than 20 years ago, there was a major battle to get it. It was heralded as a breakthrough at the time – partly due to the lack of anything else. It has become obvious that it slows mental decline for a few months but makes little effect in the long run.

The findings of another trial for some patients backed up those conclusions.

Biogen submitted a Biologics License Application to the FDA in July 2020, requesting approval of the medicine.

The FDA’s decision has been awaited by Alzheimer’s disease researchers, clinicians, and patients since then.

Support for approval of the drug

Other groups, such as the Alzheimer’s Association, have supported the drug’s approval.

The Alzheimer’s Association‘s website stated on Friday, “This is a critical time, regardless of the FDA’s final judgment. We’ve never been this close to approving an Alzheimer’s drug that could affect the disease’s development rather than just the symptoms. We can keep working together to achieve our goal of a world free of Alzheimer’s disease and other dementias.”

The drug has gotten so much attention that the Knight Alzheimer Disease Research Center at Washington University in St. Louis issued a statement on Friday stating that even if it is approved, “it will still likely take several months for the medication to pass other regulatory steps and become available to patients.”

Biogen officials told KGO-TV on Monday that the medicine will be ready to ship in about two weeks and that they have identified more than 900 facilities across the United States that they feel will be medically and commercially suitable.

Officials stated the corporation will also provide financial support to qualifying patients so that their out-of-pocket payments are as low as possible. Biogen has also pledged not to raise the price for at least the next four years.

Most Medicare customers with supplemental plans, according to the firm, will have a limited or capped co-pay.

Case studies connected to the Drug Approval

Case 1

Ann Lange, one of several Chicago-area clinical trial volunteers who received the breakthrough Alzheimer’s treatment, said,

It really offers us so much hope for a long, healthy life.

Lange, 60, has Alzheimer’s disease, which she was diagnosed with five years ago. Her memory has improved as a result of the monthly infusions, she claims.

She said,

I’d forget what I’d done in the shower, so I’d scribble ‘shampoo, conditioner, face, body’ on the door. Otherwise, I’d lose track of what I’m doing “Lange remarked. “I’m not required to do that any longer.

Case 2

Jenny Knap, 69, has been receiving infusions of the Aducanumab medication for about a year as part of two six-month research trials. She told CNN that she had been receiving treatment for roughly six months before the trial was halted in 2019, and that she had recently resumed treatment.

Knap said,

I can’t say I noticed it on a daily basis, but I do think I’m doing a lot better in terms of checking for where my glasses are and stuff like that.

When Knap was diagnosed with mild cognitive impairment, a clinical precursor to Alzheimer’s disease, in 2015, the symptoms were slight but there.

Her glasses were frequently misplaced, and she would repeat herself, forgetting previous talks, according to her husband, Joe Knap.

Joe added,

We were aware that things were starting to fall between the cracks as these instances got more often

Jenny went to the Lou Ruvo Center for Brain Health at the Cleveland Clinic in Ohio for testing and obtained her diagnosis. Jenny found she was qualified to join in clinical trials for the Biogen medicine Aducanumab at the Cleveland Clinic a few years later, in early 2017. She volunteered and has been a part of the trial ever since.

It turns out that Jenny was in the placebo category for the first year and a half, Joe explained, meaning she didn’t get the treatment.

They didn’t realize she was in the placebo group until lately because the trial was blind. Joe stated she was given the medicine around August 2018 and continued until February 2019 as the trial progressed. The trial was halted by Biogen in March 2019, but it was restarted last October, when Jenny resumed getting infusions.

Jenny now receives Aducanumab infusions every four weeks at the Cleveland Clinic, which is roughly a half-hour drive from their house, with Joe by her side. Jenny added that, despite the fact that she has only recently begun therapy, she believes it is benefiting her, combined with a balanced diet and regular exercise (she runs four miles).

The hope of Aducanumab is to halt the progression of the disease rather than to improve cognition. We didn’t appreciate any significant reduction in her condition, Jenny’s doctor, Dr. Babak Tousi, who headed Aducanumab clinical studies at the Cleveland Clinic, wrote to CNN in an email.

This treatment is unlike anything we’ve ever received before. There has never been a drug that has slowed the growth of Alzheimer’s disease, he stated, Right now, existing medications like donepezil and memantine aid with symptoms but do not slow the disease’s progression.

Jenny claims that the medicine has had no significant negative effects on her.

There was signs of some very minor bleeding in the brain at one point, which was quite some time ago. It was at very low levels, in fact, Joe expressed concern about Jenny, but added that the physicians were unconcerned.

According to Tousi, with repeated therapy, “blood vessels may become leaky, allowing fluid and red blood cells to flow out to the surrounding area,” and “micro hemorrhages have been documented in 19.1% of trial participants who got” the maximal dose of therapy”.

Jenny and Joe’s attitude on the future has improved as a result of the infusions and keeping a healthy lifestyle, according to Joe. They were also delighted to take part in the trial, which they saw as an opportunity to make a positive influence in other people’s lives.

There was this apprehension of what was ahead before we went into the clinical trial, Joe recalled. “The medical aspect of the infusion gives us reason to be optimistic. However, doing the activity on a daily basis provides us with immediate benefits.”

The drug’s final commercialization announcement

Aducanumab, which will be marketed as Aduhelm, is a monthly intravenous infusion that is designed to halt cognitive decline in patients with mild memory and thinking issues. It is the first FDA-approved medication for Alzheimer’s disease that targets the disease process rather than just the symptoms.

The manufacturer, Biogen, stated Monday afternoon that the annual list price will be $56,000. In addition, diagnostic tests and brain imaging will very certainly cost tens of thousands of dollars.

The FDA approved approval for the medicine to be used but ordered Biogen to conduct a new clinical trial, recognizing that prior trials of the medicine had offered insufficient evidence to indicate effectiveness.

Biogen Inc said on Tuesday that it expects to start shipping Aduhelm, a newly licensed Alzheimer’s medicine, in approximately two weeks and that it has prepared over 900 healthcare facilities for the intravenous infusion treatment.

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An inconvenient truth about dreams

Larry H. Bernstein, MD, FCAP, Curator



It is natural to dream. Dreaming is a flashback recording of recent occurrences associated with cleaning out the memory of daily events.  There is much written in both literature and in neuroscience as I write this.  Dreaming is both natural and perhaps also adaptive, and dreams may be distressing or unintelligible in circumstances that we view as pathological.  This is thought to be related to a loss of plasticity of the memory circuits. This occurs with mood disorders, sleep disorders with and without leg movement disorder, and with schizophrenia.

The term given by Martin Luther King, “I had a dream” is out of place under the cirumstances I describe. I am identical twin with a nonidentical triplet sister.  Our brother died more than a decade ago, prematurely aged from living with schizophrenia.  I and my sister could talk to him and understand what he said, even though it meant nothing to others. What I did not share was the total fragmentation of mental thoughts at an early age.  Both I and my sister had guilt over the situation for years. I sought psychiatric assistance that went on for years.  But I was not schizophrenic and I had a successful career by any standard, but was burdened trying to make up in achievement what was denied to my immigrant father and to my identical twin brother. It was by no means easy in the 1960s for my parents to deal with the situation, with a societal lack of understanding, a feeling of what have I done wrong, and a serious cost burden.

I went to medical school, which I had decided as a child, when I read Paul de Kruif’s Microbe Hunters.
I had a sister two years older who was a “wunder” kind, who I tried to follow.  She had a GM scholarship and set the class curve as an undergraduate in a graduate course in numbers theory.  Fortunately, my best friend, who was as brilliant as they come and a Merit Scholar college entry, cautioned not to overburden myself with the chemistry/math major that I never declared. My brother entered the hospital as I entered medical school, and the first year that would be expected to be difficult, certainly was for me.

Only in the last 5 years did I learn from extensive testing that I had a very high intelligence to match my achievement , but that I had Asperger’s.  I also learned that I had an uncommon double mutation of the hydroxymethyl-folate reductase gene that is associated nonspecifically with neurological disorders. I take methyl folate for the genetic disorder to give access of folic acid to cross the blood brain barrier.
I’m retired for several years and had enormous difficulty in retiring, and was a workaholic.  Work had great meaning and rewards for me.

I am now 74 and had a difficult 3 years with illness and hospitalization for me and my spouse of 45 years.  We moved to be near my younger daughter, son-in-law, and grandson.  This has brought great satisfaction. All the same, my asthma, sleep apnea, and general condition declined, and the move was more difficult than any I previously experienced.  I have vivid dreams that requires clonipin for relief initially.

I have had increased frequency of dreams that can be resolved.  However, with my awareness of the suicide of Robin Williams, I was given an awareness of his situation beyond what one would expect who has not seen such patients or has not experienced this.  In my situation it was worsened by added depression.  In the recent events I thought for the first time how incredible it was for my brother to have experienced this much of his schizophrenic life, even though I am not schizophrenic by any measure.

What’s in a dream?

I have had dreams before that I thought were interesting because of the people who I knew and the situations, that might have been unusual and gave me an inclination to write down.  If I collected these, it could perhaps warrant a collection of stories.  Those that are very recent have suggested that the one when I entertained my grandson is worthwhile. It was not so noxious, but it does fit the pieces together.
I watched some of the reporting of election returns of republican and democratic candidates.  I sort of tossed around and played with the exceptional 6 year old who need not be exposed to such nonsence as we are seeing.  It was early evening and to finish his limited allowable screentime, Nanny and Grandpa, and grandchild watched a children,s movie before bedtime. It was … … a takeoff on Red Ridinghood, with good cartoon figures, some recognizable voices, and an interesting storyline.  Yes, LRRH does go through the woods to see her grandma, and she meets the wolf, who goes to her grandma’s house.  Her grandma is tied up in the closet, and the woodsman, in the role of Paul Bunyan, gives a visit at the time of rescue.  The storyline becomes a detective story to cull out the events leading up to a criminal event – who stole grandma’s recipe book, with a long family line of cooking.   The grandma was an Olympic skiing champ who beets out the characters who stole her cookbooks.  I’ll say no more than that the search comes upon grandma and LRRH escape with a parachute finish and the bad guys, led by a crafty rabbit, slide down on a ski-tram into a waiting police car.  So that evening I have a dream that is a cockamaimie replay in which I am driving on the highway and enter a tunnel (like the rail in the movie), and the lane is cluttered with a wolf, and other creatures, making passage quite impossible.


I talked to my sister who called the next day. It was terrific when she said that if I had a pad and wrote them down immediately, they would form a pattern. Again, I have a dream, and I recall there was a pattern of feeling of failure. I am on Gabapentin for the restless leg. This time I have my brother (impossible) in it, I left my coat in a conference room and can’t get it immediately, and I have to return home with an exam the next day.  In a recurring pattern, my brother is to drive.  I can’t drive because of now having a diplopia from thyroid eye disease related to Grave’s disease.  The exam has two questions about plasma from unclotted blood that is spun down and serum from clotted blood. This is very basic. The pattern is related to systemic notions of failure.  My sister had a repeated pattern of rushing to get to the classes she teaches and not getting there on time (consistent with her rush rush).

I go back to bed and get another few hours of sleep. We had watched a number of Miss Marple movies recently.  In the move I had the stressful experience of going through 40 years of save photographic equipment and photography, research literature, computer stuff, ya da, ya da, ya da.   Very thorough, and tiring.  The old lady in RRH and Miss Marple were merged into a character in a story related to the corroded pipes in Flint, and a criminal search for the cause of this problem (having watched the debate). Incredibly, this character was going through the material so rapidly, uncovering clues, and I was amazed.
I was struggling to keep up.  Then I woke up. So my spouses assurances were correct.  This is actually normal dreaming.

It is disturbing, consistent with a recent New York Times article on how the brain cleans out the garbage.  I have too much garbage.  My medication does have to be adjusted.  It is perhaps not the same as my late brother’s experience. My sister’s observations have been helpful.  My brother’s dreams were recognizable to me, but not to others, but they also had patterns, but patterns that were more distorted.  If mine have been “normal”, but more frequent, this suggests a failure in the brain’s plasticity as I am aging, perhaps from from the stress in a major move.  It is perhaps to be viewed as distressing at best compared with the worst case (my brother, or Robin Williams).

This is substantiated by my remembrance of driving on Woodward avenue or the expressway in Detroit, Michigan. I grew up on 2967 Sturtevant off of Dexter Ave. My elementary school no longer exists. We moved to the Northwest section and I graduated from Mumford High School in 1961.  I lived in Trumbull, adjacent to Bridgeport, CT for 33 years, where my children grew up.  The bizarreness of my recurring dream pattern has to do with a repeated driving and confusion between Detroit and Connecticut.  I drove from Connecticut to New York for the last five years before retirement, but I failed to record these experiences.  I had two car accidents related to narcolepsy in asbout 7 years related to my sleep apnea prior to getting it treated. In the last, I went to New Jersey to see an associate and driving back to Trumbull I veered off the highway and managed to veer into a tree in the snow. Fortunately I was able to control the car at the last minute.  Fortunately, this could be much worse.








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Brain-motion mobility enhancement

Larry H. Bernstein, MD, FCAP, Curator






Implantable ‘stentrode’ to allow paralyzed patients to control an exoskeleton with their mind

UC Berkeley spinoff also announces lighter, lower-cost Phoenix exoskeleton
February 10, 2016

The “stentrode,” created by the University of Melbourne’s Vascular Bionics Laboratory, adapts an off-the-shelf self-expanding stent to include a recording electrode array. The device is delivered to the brain through blood vessels in the neck, thus avoiding many of the risks associated with traditional placement of neural implants through open-brain surgery. (credit: University of Melbourne)

A DARPA-funded research team has created a novel minimally invasive brain-machine interface and recording device that can be implanted into the brain through blood vessels, reducing the need for invasive surgery and the risks associated with breaching the blood-brain barrier when treating patients for physical disabilities and neurological disorders.


(credit: University of Melbourne)


A DARPA-funded research team has created a novel minimally invasive brain-machine interface and recording device that can be implanted into the brain through blood vessels, reducing the need for invasive surgery and the risks associated with breaching the blood-brain barrier when treating patients for physical disabilities and neurological disorders.


The new technology, developed by University of Melbourne medical researchers under DARPA’s Reliable Neural-Interface Technology (RE-NET) program, promises to give people with spinal cord injuries new hope to walk again.

The brain-machine interface consists of a stent-based electrode (stentrode), which is implanted within a blood vessel next to the brain, and records the type of neural activity that has been shown in pre-clinical trials to move limbs through an exoskeleton or to control bionic limbs.

The new device is the size of a small paperclip and will be implanted in the first in-human trial at The Royal Melbourne Hospital in 2017.

The research results, published Monday Feb. 8 in Nature Biotechnology, show the device is capable of recording high-quality signals emitted from the brain’s motor cortex without the need for open brain surgery.

“We have been able to create the world’s only minimally invasive device that is implanted into a blood vessel in the brain via a simple day procedure, avoiding the need for high risk open brain surgery,” said Thomas Oxley, principal author and neurologist at The Royal Melbourne Hospital and Research Fellow at The Florey Institute of Neurosciences and the University of Melbourne.

Stroke and spinal cord injuries are leading causes of disability, affecting 1 in 50 people. There are 20,000 Australians with spinal cord injuries, with the typical patient a 19-year old male, and about 150,000 Australians left severely disabled after stroke.



The University of Melbourne | Stentrode in action


Stentrode with 8 × 750 micrometer electrode discs (yellow arrow) self-expanding during deployment from catheter (green arrow). Scale bar, 3 mm. (credit: Thomas J. Oxley et al./Nature Biotechnology)


“The electrode array self-expands to stick to the inside wall of a vein, enabling the researchers to record local brain activity. By extracting the recorded neural signals, we can use these as commands to control wheelchairs, exoskeletons, prosthetic limbs or computers. In our first-in-human trial, that we anticipate will begin within two years, we are hoping to achieve direct brain control of an exoskeleton for three people with paralysis,” he said.

Thought control

“Currently, exoskeletons are controlled by manual manipulation of a joystick to switch between the various elements of walking — stand, start, stop, turn. The stentrode will be the first device that enables direct thought control of these devices.”

Professor Clive May, neurophysiologist at The Florey, said the data from the pre-clinical study highlighted that the implantation of the device was safe for long-term use. “Our study also showed that it was safe and effective to implant the device via angiography, which is minimally invasive compared with the high risks associated with open-brain surgery.

The authors note that “avoiding direct contact with cortical neurons may mitigate brain trauma and chronic local inflammation,” subject to additional evaluation.



The University of Melbourne | Stentrode: Moving with the power of thought


In addition to DARPA, the research was supported by Australia’s National Health and Medical Research Council, the U.S. Office of Naval Research Global, The Australian Defence Health Foundation, The Brain Foundation, and The Royal Melbourne Hospital Neuroscience Foundation.

Lighter, more agile exoskeleton helps the paralyzed to walk


Steven Sanchez, who was paralyzed from the waist down after a BMX accident, wears SuitX’s light, more agile Phoenix exoskeleton. (credit: SuitX)


Meanwhile, in related research (also based on initial funding from DARPA), SuitX, a spinoff of UC Berkeley’s Robotics and Human Engineering Laboratory robotics lab, introduced last week the Phoenix — a new lighter, more agile and lower-cost manually controlled exoskeleton.

The Phoenix is lightweight and has two motors at the hips and electrically controlled tension settings that tighten when the wearer is standing and swing freely when they’re walking. Users can control the movement of each leg and walk up to 1.1 miles per hour by pushing buttons integrated into a pair of crutches. It’s powered for up to eight hours by a battery pack worn in a backpack.

Developed from the Berkeley Lower Extremity Exoskeleton (BLEEX), the Phoenix is one of the lightest and most accessible exoskeletons available, according to SuitX. It can be adjusted to fit varied weights, heights, and leg sizes and can be used for a range of mobility hindrances. At $40,000, it’s about the half the cost of other exoskeletons that help restore mobility.


Abstract of Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity

High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.




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optimal deep-brain near-infrared imaging wavelength determined

Larry H. Bernstein, MD, FCAP, Curator



‘Golden window’ wavelength range for optimal deep-brain near-infrared imaging determined




Rayleigh scattering causes the reddening of the sun at sunset — an example of how longer wavelengths (yellow and red compared to blue in blue sky) penetrate matter (dust at sunset) better. (credit: Wikipedia/CC)


Researchers at The City College of New York (CCNY) have determined the optimal wavelengths for bioimaging of the brain at longer near-infrared wavelengths, which permit deeper imaging.

Near-infrared (NIR) radiation has been used for one- and two-photon fluorescence imaging at near-infrared wavelengths of 650–950 nm (nanometers) for deep brain imaging, but it is limited in penetration depth. (The CCNY researchers dubbed this Window I, also known as the therapeutic window.)

Longer infrared wavelengths penetrate deeper but are limited by Rayleigh and Mie scattering, which blur images, and absorption, which reduces the number of available photons (brightness). These limitations are based on the lack of suitable CMOS semiconductor imaging detectors or femtosecond laser sources.

The new CCNY study, led by biomedical engineer Lingyan Shi, studied three new optical windows in the near-infrared (NIR) region, in addition to Window I, for high-resolution deep brain imaging.

Their study built on a prior CCNY study* in 2014 using detectors based on indium gallium arsenide (GaAs) or indium antimonide-(InSb) and a femtosecond excitation source of IMRA fiber laser** to image rat brain tissue in window II (1,100– 1,350 nm), window III (1,600–1,870 nm), and window IV (1600 nm to 1870 nm, centered at 2,200 nm).



Absorbance for four windows at four brain-tissue thicknesses (credit: Lingyan Shi et al./J. Biophotonics)


The new CCNY research investigated the optimal wavelength band and optical properties of brain tissue with NIR, including the total attenuation coefficient (μt), absorption coefficient (μa), reduced scattering coefficient (μ0 s), and the scattering anisotropy coefficient (g) in these optical windows. The purpose of the study was to determine an optimal optical window in NIR in the 650 nm to 2500 nm range to reduce scattering, achieve optimal absorption, and reduce noise for deep-brain tissue imaging.


Golden Window: optimal wavelength range

Peak transmittance T (%) measured with each optical window for brain tissues with four thicknesses. Window III had the highest transmittance percentage for each of the thicknesses, followed by windows II and IV. (credit: Lingyan Shi et al./J. Biophotonics)

The researchers found that the “Golden Window” (1600 nm to 1870 nm) is an optimal wavelength range for light penetration in brain tissue, followed by Windows II and IV.

“This is a first for brain imaging and proved theoretically and experimentally that deep imaging of the brain is possible using light at longer wavelengths. It demonstrates these windows’ potential for deeper brain tissue imaging due to the reduction of scattering that causes blurring,” said Shi, a research associate in City College’s Institute for Ultrafast Spectroscopy and Lasers, and the biology department.

Published by the Journal of Biophotonics, her study sheds light on the development of the next generation of microscopy imaging technique, in which the “Golden Window” may be utilized for high-resolution deeper brain imaging. The next step in the research is in vivo imaging in mice using Golden Window wavelength light.

Shi’s team included Distinguished Professor of Physics Robert R. Alfano and Adrian Rodriguez-Contreras, an assistant professor of biology. Shi earned a Ph.D. in biomedical engineering from CCNY’s Grove School of Engineering in 2014.

* L. A. Sordillo, Y. Pu, S. Pratavieira, Y. Budansky, and R. R. Alfano, J. Biomed. Opt. 19, 056004 (2014) [link].

** Excitation wavelength 1680 nm, power > 200 mW, pulse width 100 fs, and 50 MHz repetition rate.



Abstract of Transmission in near-infrared optical windows for deep brain imaging

Near-infrared (NIR) radiation has been employed using one- and two-photon excitation of fluorescence imaging at wavelengths 650–950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR-low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100–1,350 nm), third (III, 1,600–1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I.

Lingyan Shi, Laura A. Sordillo, Adrián Rodríguez-Contreras, Robert Alfano.
Journal of Biophotonics, 2015;   DOI: http://dx.doi.org/10.1002/jbio.201500192


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