Date:
February 21, 2017

Source:
Stanford University Medical Center

Summary:
A brain-to-computer hookup can enable people with paralysis to type via direct brain control at the highest speeds and accuracy levels reported to date, a clinical research publication has demonstrated.

 

Stanford’s Jaimie Henderson and Krishna Shenoy are part of a consortium working on an investigational brain-to-computer hookup.
Credit: Paul Sakuma

 

 

A clinical research publication led by Stanford University investigators has demonstrated that a brain-to-computer hookup can enable people with paralysis to type via direct brain control at the highest speeds and accuracy levels reported to date.

The report involved three study participants with severe limb weakness — two from amyotrophic lateral sclerosis, also called Lou Gehrig’s disease, and one from a spinal cord injury. They each had one or two baby-aspirin-sized electrode arrays placed in their brains to record signals from the motor cortex, a region controlling muscle movement. These signals were transmitted to a computer via a cable and translated by algorithms into point-and-click commands guiding a cursor to characters on an onscreen keyboard.

Each participant, after minimal training, mastered the technique sufficiently to outperform the results of any previous test of brain-computer interfaces, or BCIs, for enhancing communication by people with similarly impaired movement. Notably, the study participants achieved these typing rates without the use of automatic word-completion assistance common in electronic keyboarding applications nowadays, which likely would have boosted their performance.

One participant, Dennis Degray of Menlo Park, California, was able to type 39 correct characters per minute, equivalent to about eight words per minute.

‘A major milestone’

This point-and-click approach could be applied to a variety of computing devices, including smartphones and tablets, without substantial modifications, the Stanford researchers said.

“Our study’s success marks a major milestone on the road to improving quality of life for people with paralysis,” said Jaimie Henderson, MD, professor of neurosurgery, who performed two of the three device-implantation procedures. The third took place at Massachusetts General Hospital.

Henderson and Krishna Shenoy, PhD, professor of electrical engineering, are co-senior authors of the study, which will be published online Feb. 21 in eLife. The lead authors are former postdoctoral scholar Chethan Pandarinath, PhD, and postdoctoral scholar Paul Nuyujukian, MD, PhD, both of whom spent well over two years working full time on the project at Stanford.

“This study reports the highest speed and accuracy, by a factor of three, over what’s been shown before,” said Shenoy, a Howard Hughes Medical Institute investigator who’s been pursuing BCI development for 15 years and working with Henderson since 2009. “We’re approaching the speed at which you can type text on your cellphone.”

“The performance is really exciting,” said Pandarinath, who now has a joint appointment at Emory University and the Georgia Institute of Technology as an assistant professor of biomedical engineering. “We’re achieving communication rates that many people with arm and hand paralysis would find useful. That’s a critical step for making devices that could be suitable for real-world use.”

Shenoy’s lab pioneered the algorithms used to decode the complex volleys of electrical signals fired by nerve cells in the motor cortex, the brain’s command center for movement, and convert them in real time into actions ordinarily executed by spinal cord and muscles.

“These high-performing BCI algorithms’ use in human clinical trials demonstrates the potential for this class of technology to restore communication to people with paralysis,” said Nuyujukian.

Life-changing accident

Millions of people with paralysis reside in the United States. Sometimes their paralysis comes gradually, as occurs in ALS. Sometimes it arrives suddenly, as in Degray’s case.

Now 64, Degray became quadriplegic on Oct. 10, 2007, when he fell and sustained a life-changing spinal-cord injury. “I was taking out the trash in the rain,” he said. Holding the garbage in one hand and the recycling in the other, he slipped on the grass and landed on his chin. The impact spared his brain but severely injured his spine, cutting off all communication between his brain and musculature from the head down.

“I’ve got nothing going on below the collarbones,” he said.

Degray received two device implants at Henderson’s hands in August 2016. In several ensuing research sessions, he and the other two study participants, who underwent similar surgeries, were encouraged to attempt or visualize patterns of desired arm, hand and finger movements. Resulting neural signals from the motor cortex were electronically extracted by the embedded recording devices, transmitted to a computer and translated by Shenoy’s algorithms into commands directing a cursor on an onscreen keyboard to participant-specified characters.

The researchers gauged the speeds at which the patients were able to correctly copy phrases and sentences — for example, “The quick brown fox jumped over the lazy dog.” Average rates were 7.8 words per minute for Degray and 6.3 and 2.7 words per minute, respectively, for the other two participants.

A tiny silicon chip

The investigational system used in the study, an intracortical brain-computer interface called the BrainGate Neural Interface System*, represents the newest generation of BCIs. Previous generations picked up signals first via electrical leads placed on the scalp, then by being surgically positioned at the brain’s surface beneath the skull.

An intracortical BCI uses a tiny silicon chip, just over one-sixth of an inch square, from which protrude 100 electrodes that penetrate the brain to about the thickness of a quarter and tap into the electrical activity of individual nerve cells in the motor cortex.

Henderson likened the resulting improved resolution of neural sensing, compared with that of older-generation BCIs, to that of handing out applause meters to individual members of a studio audience rather than just stationing them on the ceiling, “so you can tell just how hard and how fast each person in the audience is clapping.”

Shenoy said the day will come — closer to five than 10 years from now, he predicted — when a self-calibrating, fully implanted wireless system can be used without caregiver assistance, has no cosmetic impact and can be used around the clock.

“I don’t see any insurmountable challenges.” he said. “We know the steps we have to take to get there.”

Degray, who continues to participate actively in the research, knew how to type before his accident but was no expert at it. He described his newly revealed prowess in the language of a video game aficionado.

“This is like one of the coolest video games I’ve ever gotten to play with,” he said. “And I don’t even have to put a quarter in it.”

The study’s results are the culmination of a long-running collaboration between Henderson and Shenoy and a multi-institutional consortium called BrainGate. Leigh Hochberg, MD, PhD, a neurologist and neuroscientist at Massachusetts General Hospital, Brown University and the VA Rehabilitation Research and Development Center for Neurorestoration and Neurotechnology in Providence, Rhode Island, directs the pilot clinical trial of the BrainGate system and is a study co-author.

“This incredible collaboration continues to break new ground in developing powerful, intuitive, flexible neural interfaces that we all hope will one day restore communication, mobility and independence for people with neurologic disease or injury,” said Hochberg.


Story Source:

Materials provided by Stanford University Medical Center. Original written by Bruce Goldman. Note: Content may be edited for style and length.


Journal Reference:

  1. Chethan Pandarinath Paul Nuyujukian Christine H Blabe Brittany L Sorice Jad Saab Francis R Willett Leigh R Hochberg Krishna V Shenoy Jaimie M Henderson. High performance communication by people with paralysis using an intracortical brain-computer interface. eLife, February 2017 DOI: 10.7554/eLife.18554

 

Source: Stanford University Medical Center. “Brain-computer interface advance allows fast, accurate typing by people with paralysis.” ScienceDaily. ScienceDaily, 21 February 2017. <www.sciencedaily.com/releases/2017/02/170221080457.htm>.

Date:
February 20, 2017

Source:
Arizona State University

Summary:
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices. Much like flipping your light switch at home — only on a scale 1,000 times smaller than a human hair — a team has now developed the first controllable DNA switch to regulate the flow of electricity within a single, atomic-sized molecule.

 

Tao’s group, modified just one of DNA’s iconic double helix chemical letters, abbreviated as A, C, T or G, with another chemical group, called anthraquinone (Aq). Anthraquinone is a three-ringed carbon structure that can be inserted in between DNA base pairs but contains what chemists call a redox group (short for reduction, or gaining electrons or oxidation, losing electrons). The modified Aq-DNA helix could now help it perform the switch, slipping comfortably in between the rungs that make up the ladder of the DNA helix, and bestowing it with a new found ability to reversibly gain or lose electrons.
Credit: Biodesign Institute, Arizona State University

 

 

DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.

Much like flipping your light switch at home — only on a scale 1,000 times smaller than a human hair — an ASU-led team has now developed the first controllable DNA switch to regulate the flow of electricity within a single, atomic-sized molecule. The new study, led by ASU Biodesign Institute researcher Nongjian Tao, was published in the advanced online journal Nature Communications.

“It has been established that charge transport is possible in DNA, but for a useful device, one wants to be able to turn the charge transport on and off. We achieved this goal by chemically modifying DNA,” said Tao, who directs the Biodesign Center for Bioelectronics and Biosensors and is a professor in the Fulton Schools of Engineering. “Not only that, but we can also adapt the modified DNA as a probe to measure reactions at the single-molecule level. This provides a unique way for studying important reactions implicated in disease, or photosynthesis reactions for novel renewable energy applications.”

Engineers often think of electricity like water, and the research team’s new DNA switch acts to control the flow of electrons on and off, just like water coming out of a faucet.

Previously, Tao’s research group had made several discoveries to understand and manipulate DNA to more finely tune the flow of electricity through it. They found they could make DNA behave in different ways — and could cajole electrons to flow like waves according to quantum mechanics, or “hop” like rabbits in the way electricity in a copper wire works — creating an exciting new avenue for DNA-based, nano-electronic applications.

Tao assembled a multidisciplinary team for the project, including ASU postdoctoral student Limin Xiang and Li Yueqi performing bench experiments, Julio Palma working on the theoretical framework, with further help and oversight from collaborators Vladimiro Mujica (ASU) and Mark Ratner (Northwestern University).

To accomplish their engineering feat, Tao’s group, modified just one of DNA’s iconic double helix chemical letters, abbreviated as A, C, T or G, with another chemical group, called anthraquinone (Aq). Anthraquinone is a three-ringed carbon structure that can be inserted in between DNA base pairs but contains what chemists call a redox group (short for reduction, or gaining electrons or oxidation, losing electrons).

These chemical groups are also the foundation for how our bodies’ convert chemical energy through switches that send all of the electrical pulses in our brains, our hearts and communicate signals within every cell that may be implicated in the most prevalent diseases.

The modified Aq-DNA helix could now help it perform the switch, slipping comfortably in between the rungs that make up the ladder of the DNA helix, and bestowing it with a new found ability to reversibly gain or lose electrons.

Through their studies, when they sandwiched the DNA between a pair of electrodes, they careful controlled their electrical field and measured the ability of the modified DNA to conduct electricity. This was performed using a staple of nano-electronics, a scanning tunneling microscope, which acts like the tip of an electrode to complete a connection, being repeatedly pulled in and out of contact with the DNA molecules in the solution like a finger touching a water droplet.

“We found the electron transport mechanism in the present anthraquinone-DNA system favors electron “hopping” via anthraquinone and stacked DNA bases,” said Tao. In addition, they found they could reversibly control the conductance states to make the DNA switch on (high-conductance) or switch-off (low conductance). When anthraquinone has gained the most electrons (its most-reduced state), it is far more conductive, and the team finely mapped out a 3-D picture to account for how anthraquinone controlled the electrical state of the DNA.

For their next project, they hope to extend their studies to get one step closer toward making DNA nano-devices a reality.

“We are particularly excited that the engineered DNA provides a nice tool to examine redox reaction kinetics, and thermodynamics the single molecule level,” said Tao.


Story Source:

Materials provided by Arizona State University. Note: Content may be edited for style and length.


Journal Reference:

  1. Limin Xiang, Julio L. Palma, Yueqi Li, Vladimiro Mujica, Mark A. Ratner, Nongjian Tao. Gate-controlled conductance switching in DNA. Nature Communications, 2017; 8: 14471 DOI: 10.1038/ncomms14471

 

Source: Arizona State University. “Switched-on DNA: Sparking nano-electronic applications.” ScienceDaily. ScienceDaily, 20 February 2017. <www.sciencedaily.com/releases/2017/02/170220084156.htm>.

JAMA Publishes Results of the First FDA Approved Product that Used eSource (Target e*CTR®) to Collect and Store Real Time Data in the Clinic

 

Many years ago a very senior executive at Pfizer told me (Jules Mitchel, a proud Pfizer alumnus) that if you can just get a product approved that used your paperless solution, we will all jump in. He added that Big Pharma will not take the chance itself, but you guys are “crazy enough to even try, so just do it.“  Well, not only did we do it, but the results of the clinical program was just published in JAMA.

 

On 14 February 2017, JAMA, the Journal of the American Medical Association, (volume 317:606-614) published a paper entitled “Association Between Use of a Scalp Cooling Device and Alopecia After Chemotherapy for Breast Cancer.“ Target is honored to have managed and executed this entire program, and to be co-authors on this ground-breaking treatment for women undergoing breast cancer chemotherapy.

 

From the clinical research operational perspective, this study was executed using Target Health’s patented, web-based, eSource solution, Target eClinical Trial Record (Target e*CTR®), which was fully integrated with Target e*CRF®, Target Health’s proprietary EDC system. Both Target Health and 3 major medical centers were subject to FDA inspections which were passed with no findings related to Target Health’s paperless clinical trial solution, and Target Health’s approach to risk based monitoring and Quality by Design. There was only one minor finding at one of the research sites related to GCP, as nothing is perfect.

 

Related articles include: Regulatory Considerations when Designing and Running 21st Century Paperless Clinical Trials and eSource Records in Clinical Research, and more papers can be found on our website.

 

Sunrise in NYC

 

Every once in a while, the early bird catches the worm. Another spectacular sun rise looking towards Europe.

 

Sunrise of the 24th Floor©Target Health Inc.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

Washi Paper -Cultural Heritage and Artistic Creativity, January 26 – February 24, 2017.

 

Art exhibitions at the Nippon Club, New York City

 

By Mui Ying Kwan, Cultural LiasonTarget Health

 

This month, I attended the opening reception and lecture on “Washi Paper, A cultural Heritage and Artistic Creativity“ at the Nippon Club. The program began with an informative lecture given by Professor Koji Shibazaki on washi paper, a traditional craft and art form that played a crucial role in Japanese culture since the eight Century. Prof. Shibazaki is from the design and craft department at Aichi University of Fine Arts in Japan. Professor Shibazaki spoke about the history of papermaking which was introduced to Japan from China in the 7th century by Buddhist monks who made paper for writing sutras. This is how Washi paper was produced all over Japan. Made from natural ingredients and indigenous raw materials, washi paper capture the unique climate and other geographical characteristics of the place where the paper was produce. However, in modern times, the tradition and symbolism of handmade washi is fast becoming a lost art as modern technologies allow for washi paper to be manufactured at a much lower cost and lower quality.

 

The purpose of the Nippon exhibition is to re-discover the beauty and functionality of washi paper and re-introduce it through a variety of contemporary artistic interpretations of washi paper such as origami sculptures and calligraphy.

 

After the lecture, Mr. Mohri Suzuki, a student at Aichi University gave an incredible and dramatic Calligraphy performance which took every one’s breath away because of the grand scale. After the performance, I had a chance to meet to meet Mr. Suzuki who took some great photos with Target Health personnel next to his Calligraphy art. Next everyone moved to the second floor exhibition space, featuring origami sculptures made of washi paper and Calligraphy art by are Mohri Suzuki and professor Koji Shibazaki and Kiyoharu Uchiumi from Aichi University. All the windows are covered in washi paper in order to create a profound atmosphere of darkness so that the natural light emanated from the washi lantern. Some of the sculptures are constructed with cut gold leaf and lanterns made from washi paper inspired by lanterns from the Edo period Japan.

 

As we face worsening environmental problems today, the washi paper exhibition was a wonderful and inspiring event. Target Health is proud support art made with natural ingredients.

 

 

Photos with captions of “Washi Paper -Cultural Heritage and Artistic Creativity“ – exhibition

January 26 – February 24, 2017

 

Nippon Club, New York City: Mr. Mohri Suzuki is a student and artist at Aichi University, Japan, in traditional Japanese attire, gave an incredible and dramatic Calligraphy performance, using washi paper on a grand scale. Mr. Mohri Suzuki continued his exploration of the art of Calligraphy through the physical act of making washi paper.

 

Nippon Club, New York City: Ms. Kiyoharu Uchiumi is also a student and artist at Aichi University, Japan. She explores art using Another form of origami is called origata. A tradition established by the samurai class during the 15th century, origata is the art of wrapping gifts in paper, and was often used as decoration for special ceremonies. To the left of Ms. Kiyoharu Uchiumi, is Target Health Cultural Liaison, Mui Ying Kwan, with THI for 19 years and to the right, is Violet Arlequin, Data Manager at Target Health Inc. for 17 years.

 

Nippon Club, New York City: “Nightface series“ by Professor Koji Shibazaki from the design and craft department at Aichi University of Fine Arts. He uses the unique and transformative translucency of layered washi paper to explore the subtle beauty of Japanese illumination from the Edo period through lanterns made with washi paper.

 

Nippon Club, New York City: Mr. Mohri Suzuki is a student and artist at Aichi University continued his exploration of the art of Calligraphy through the physical act of making washi paper.

 

Nippon Club, New York City: Mr. Mohri Suzuki a student and artist at Aichi University, Japan, in traditional Japanese attire, gave an incredible and dramatic Calligraphy performance, using washi paper on a grand scale.

 

Nippon Club, New York City: Mr. Mohri Suzuki a student and artist at Aichi University, Japan, in traditional Japanese attire, after an incredible and dramatic Calligraphy performance, using washi paper on a grand scale.

 

Nippon Club, New York City: Professor Koji Shibazaki from the design and craft department at Aichi University of Fine Arts in Japan gives a lecture on the history of washi paper, a traditional craft and art form that played a crucial role in Japanese culture since the eight Century.

 

Nippon Club New York City: A variety of classic Japanese art forms reinterpreted by contemporary artists. washi paper will give rise to a resurgence of this traditional craft through new and creative applications such as origami sculptures and calligraphy.

 

Nippon Club, New York City: Handmade washi paper and calligraphy by Mohri Suzuki.

QUIZ

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MRIs Predict Which High-Risk Babies Will Develop Autism as Toddlers

Magnetic resonance angiography. Source: Ofirglazer at English Wikipedia, commons.wikimedia.org

 

Magnetic resonance angiography (MRA), in the image above, generates pictures of the arteries to evaluate them for stenosis (abnormal narrowing) or aneurysms (vessel wall dilatations, at risk of rupture). MRA is often used to evaluate the 1) ___ of the neck and brain, the thoracic and abdominal aorta, the renal arteries, and the legs (called a “run-off“). A variety of techniques can be used to generate the pictures, such as administration of a paramagnetic contrast agent (gadolinium) or using a technique known as “flow-related enhancement“ (e.g., 2D and 3D time-of-flight sequences), where most of the signal on an image is due to blood that recently moved into that plane, see also FLASH MRI. Techniques involving phase accumulation (known as phase contrast angiography) can also be used to generate flow velocity maps easily and accurately. Magnetic resonance venography (MRV) is a similar procedure that is used to image veins. In this method, the tissue is now excited inferiorly, while the signal is gathered in the plane immediately superior to the excitation plane – thus imaging the venous blood that recently moved from the excited plane. Magnetic 2) ___ spectroscopy (MRS) is used to measure the levels of different metabolites in body tissues. The MR signal produces a spectrum of resonances that corresponds to different molecular arrangements of the isotope being “excited“. This signature is used to diagnose certain metabolic disorders, especially those affecting the brain, and to provide information on tumor metabolism.

 

At the University of North Carolina (Chapel Hill), a first-of-its-kind study, published in Nature, used magnetic resonance imaging (MRI) to image the of infants, and then researchers used brain measurements and a computer algorithm to accurately predict autism before 3) ___ set in. Using MRI in 4) ___ with older siblings with autism, researchers from around the country were able to correctly predict 80% of those infants who would later meet criteria for autism at two years of age. “Our study shows that early brain development biomarkers could be very useful in identifying babies at the highest risk for autism before behavioral symptoms emerge,“ said senior author Joseph Piven, MD, the Thomas E. Castelloe Distinguished Professor of Psychiatry at the University of North Carolina-Chapel Hill. “Typically, the earliest an autism diagnosis can be made is between ages two and three. But for babies with older autistic siblings, our imaging approach may help predict during the first year of life which babies are most likely to receive an 5) ___ diagnosis at 24 months.“ This research project included hundreds of children from across the country and was led by researchers at the Carolina Institute for Developmental Disabilities (CIDD) at the University of North Carolina, where Piven is director. The project’s other clinical sites included the University of Washington, Washington University in St. Louis, and The Children’s Hospital of Philadelphia. Other key collaborators are McGill University, the University of Alberta, the University of Minnesota, the College of Charleston, and New York University. “This study could not have been completed without a major commitment from these families, many of whom flew in to be part of this,“ said first author Heather Hazlett, PhD, assistant professor of psychiatry at the UNC School of Medicine and a CIDD researcher. “We are still enrolling families for this study, and we hope to begin work on a similar project to replicate our findings.“

 

People with ASD 6) ___ ___ ___ have characteristic social deficits and demonstrate a range of ritualistic, repetitive and stereotyped behaviors. It is estimated that one out of 68 children develop autism in the United States. For infants with older siblings with autism, the risk may be as high as 20 out of every 100 births. There are about 3 million people with autism in the United States and tens of millions around the world. Despite much research, it has been impossible to identify those at ultra-high 7) ___ for autism prior to 24 months of age, which is the earliest time when the hallmark behavioral characteristics of ASD can be observed and a diagnosis made in most children. For the study, it was found that the babies who developed autism experienced a hyper-expansion of brain surface area from six to 12 months, as compared to babies who had an older sibling with autism but did not themselves show evidence of the condition at 24 months of age. Increased growth rate of surface area in the first year of life was linked to increased growth rate of overall brain volume in the second year of life. Brain overgrowth was tied to the emergence of autistic social deficits in the second year. Previous behavioral studies of infants who later developed autism — who had older siblings with autism -revealed that social behaviors typical of autism emerge during the 8) ___ year of life. The researchers then took these data — MRIs of brain volume, surface area, cortical thickness at 6 and 12 months of age, and sex of the infants — and used a computer program to identify a way to classify babies most likely to meet criteria for autism at 24 months of age. The computer program developed the best algorithm to accomplish this, and the researchers applied the algorithm to a separate set of study participants. The researchers found that brain differences at 6 and 12 months of age in infants with older siblings with autism correctly predicted eight out of ten infants who would later meet criteria for autism at 24 months of age in comparison to those infants with older ASD siblings who did not meet criteria for autism at 24 months. “This means we potentially can identify infants who will later develop autism, before the symptoms of autism begin to consolidate into a diagnosis,“ Piven said. If parents have a child with autism and then have a second child, such a test might be clinically useful in identifying infants at highest risk for developing this condition. The idea would be to then intervene ‘pre-symptomatically’ before the emergence of the defining symptoms of autism. Research could then begin to examine the effect of interventions on children during a period before the syndrome is present and when the brain is most malleable. Such interventions may have a greater chance of improving outcomes than treatments started after diagnosis. “Putting this into the larger context of neuroscience research and treatment, there is currently a big push within the field of neurodegenerative diseases to be able to detect the biomarkers of these conditions before patients are diagnosed, at a time when preventive efforts are possible,“ Piven said. “In Parkinson’s for instance, we know that once a person is diagnosed, they’ve already lost a substantial portion of the dopamine receptors in their 9) ___, making treatment less effective.“ Piven said the idea with autism is similar; once autism is diagnosed at age 2-3 years, the brain has already begun to change substantially. “We haven’t had a way to detect the biomarkers of autism before the condition sets in and symptoms develop,“ he said. “Now we have very promising leads that suggest this may in fact be possible.“ In addition to new algorithms todetect autism in toddlers, there have been additional advances in MRI technology, like diffusion. Diffusion MRI measures the diffusion of water molecules in biological tissues. Clinically, diffusion MRI is useful for the diagnoses of conditions (e.g., stroke) or neurological disorders (e.g., multiple sclerosis), and helps better understand the connectivity of white matter axons in the central nervous system. In an isotropic medium (inside a glass of water for example), water molecules naturally move randomly according to turbulence and Brownian motion. In biological tissues however, where the Reynolds number is low enough for laminar flow, the diffusion may be anisotropic. For example, a molecule inside the axon of a neuron has a low probability of crossing the myelin membrane. Therefore, the molecule moves principally along the axis of the neural fiber. If it is known that molecules in a particular voxel diffuse principally in one direction, the assumption can be made that the majority of the fibers in this area are parallel to that direction. The recent development of diffusion tensor imaging (DTI) enables diffusion to be measured in multiple directions, and the fractional anisotropy in each direction to be calculated for each voxel. This enables researchers to make brain maps of fiber directions to examine the connectivity of different regions in the brain (using tractography) or to examine areas of neural degeneration and demyelination in diseases like multiple sclerosis. Another application of diffusion MRI is diffusion-weighted imaging (DWI). Following an ischemic 10) ___, DWI is highly sensitive to the changes occurring in the lesion. It is speculated that increases in restriction (barriers) to water diffusion, as a result of cytotoxic edema (cellular swelling), is responsible for the increase in signal on a DWI scan. The DWI enhancement appears within 5-10 minutes of the onset of stroke symptoms (as compared to computed tomography, which often does not detect changes of acute infarct for up to 4-6 hours) and remains for up to two weeks. Coupled with imaging of cerebral perfusion, researchers can highlight regions of “perfusion/diffusion mismatch“ that may indicate regions capable of salvage by reperfusion therapy. Like many other specialized applications, this technique is usually coupled with a fast image acquisition sequence, such as echo planar imaging sequence.  Sources: University of North Carolina Health Care; ScienceDaily.com

 

ANSWERS: 1) arteries; 2) resonance; 3) symptoms; 4) infants; 5) autism; 6) Autism Spectrum Disorder; 7) risk; 8) second; 9) brain; 10) stroke

A Short History of MRIs

MRI Scanner Mark One. The first MRI scanner to be built and used, in Aberdeen Royal Infirmary in Scotland. Source: Andy Gaskell – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=54271471

 

U.S. President George W. Bush with the six 2003 American Nobel laureates in the Oval Office. From left to right, Dr. Roderick MacKinnon, New York City (chemistry); Dr. Anthony Leggett, Urbana, Illinois (physics); Dr. Robert Engle, New York City (economics); Dr. Alexei Abrikosov, Argonne, Illinois (physics); Dr. Peter Agre, Baltimore, Maryland (chemistry); and Dr. Paul Lauterbur, Urbana, Illinois (physiology/medicine). Source: This work is in the public domain in the United States because it is a work prepared by an officer or employee of the United States Government as part of that person’s official duties under the terms of Title 17, Chapter 1, Section 105 of the US Code; Wikipedia Commons

 

Magnetic resonance imaging was invented by Paul C. Lauterbur in September 1971; he published the theory behind it in March 1973. The factors leading to image contrast (differences in tissue relaxation time values) had been described nearly 20 years earlier by Erik Odeblad (physician and scientist) and Gunnar Lindstrom. In 1950, spin echoes were first detected by American, Erwin Hahn and in 1952, Herman Carr produced a one-dimensional NMR spectrum as reported in his Harvard PhD thesis. In the Soviet Union, Vladislav Ivanov filed (in 1960) a document with the USSR State Committee for Inventions and Discovery at Leningrad for a Magnetic Resonance Imaging device, although this was not approved until the 1970s. By 1959, Jay Singer had studied blood flow by NMR relaxation time measurements of blood in living humans. Such measurements were not introduced into common medical practice until the mid-1980s, although a patent for a whole-body NMR machine to measure blood flow in the human body was already filed by Alexander Ganssen in early 1967. In the 1960s and 1970s the results of a very large amount of work on relaxation, diffusion, and chemical exchange of water in cells and tissues of all sorts appeared in the scientific literature. In 1967, Ligon reported the measurement of NMR relaxation of water in the arms of living human subjects. In 1968, Jackson and Langham published the first NMR signals from a living animal.

 

Raymond Damadian’s “Apparatus and method for detecting cancer in tissue“ Source: This patent drawing by Raymond Damadian, belongs to a US govt Patent number 3789832 filed 17 March 1972, issued Feb 5, 1974. Image is from the US Patent and Trademark Office.

 

 

In a March 1971 paper in the journal Science, Raymond Damadian, an Armenian-American physician and professor at the Downstate Medical Center State University of New York (SUNY), reported that tumors and normal tissue can be distinguished in vivo by nuclear magnetic resonance (“NMR“). He suggested that these differences could be used to diagnose cancer, though later research would find that these differences, while real, are too variable for diagnostic purposes. Damadian’s initial methods were flawed for practical use, relying on a point-by-point scan of the entire body and using relaxation rates, which turned out not to be an effective indicator of cancerous tissue. While researching the analytical properties of magnetic resonance, Damadian created a hypothetical magnetic resonance cancer-detecting machine in 1972. He filed the first patent for such a machine, U.S. Patent 3,789,832 on March 17, 1972, which was later issued to him on February 5, 1974. Zenuemon Abe and his colleagues applied the patent for targeted NMR scanner, U.S. Patent 3,932,805 on 1973. They published this technique in 1974. Damadian claims to have invented the MRI. The US National Science Foundation notes “The patent included the idea of using NMR to ‘scan’ the human body to locate cancerous tissue.“ However, it did not describe a method for generating pictures from such a scan or precisely how such a scan might be done.

 

Meanwhile, Paul Lauterbur at Stony Brook University expanded on Carr’s technique and developed a way to generate the first MRI images, in 2D and 3D, using gradients. In 1973, Lauterbur published the first nuclear magnetic resonance image and the first cross-sectional image of a living mouse in January 1974. In the late 1970s, Peter Mansfield, a physicist and professor at the University of Nottingham, England, developed the echo-planar imaging (EPI) technique that would lead to scans taking seconds rather than hours and produce clearer images than Lauterbur had. Damadian, along with Larry Minkoff and Michael Goldsmith, obtained an image of a tumor in the thorax of a mouse in 1976. They also performed the first MRI body scan of a human being on July 3, 1977, studies they published in 1977. In 1979, Richard S. Likes filed a patent on k-space U.S. Patent 4,307,343. During the 1970s a team led by John Mallard built the first full-body MRI scanner at the University of Aberdeen. On August 28,1980 they used this machine to obtain the first clinically useful image of a patient’s internal tissues using MRI, which identified a primary tumor in the patient’s chest, an abnormal liver, and secondary cancer in his bones. This machine was later used at St Bartholomew’s Hospital, in London, from 1983 to 1993. Mallard and his team are credited for technological advances that led to the widespread introduction of MRI.

 

In 1975, the University of California, San Francisco Radiology Department founded the Radiologic Imaging Laboratory (RIL). With the support of Pfizer, Diasonics, and later Toshiba America MRI, the lab developed new imaging technology and installed systems in the US and worldwide. In 1981 RIL researchers, including Leon Kaufman and Lawrence Crooks, published Nuclear Magnetic Resonance Imaging in Medicine. In the 1980s the book was considered the definitive introductory textbook to the subject. In 1980 Paul Bottomley joined the GE Research Center in Schenectady, NY. His team ordered the highest field-strength magnet then available – a 1.5 T system – and built the first high-field device, overcoming problems of coil design, RF penetration and signal-to-noise ratio to build the first whole-body MRI/MRS scanner. The results translated into the highly successful 1.5 T MRI product-line, with over 20,000 systems in use today. In 1982, Bottomley performed the first localized MRS in the human heart and brain. After starting a collaboration on heart applications with Robert Weiss at Johns Hopkins, Bottomley returned to the university in 1994 as Russell Morgan Professor and director of the MR Research Division. Although MRI is most commonly performed at 1.5 T, higher fields such as 3 T are gaining more popularity because of their increased sensitivity and resolution. In research laboratories, human studies have been performed at up to 9.4 T and animal studies have been performed at up to 21.1 T.

 

Reflecting the fundamental importance and applicability of MRI in medicine, Paul Lauterbur of the University of Illinois at Urbana-Champaign and Sir Peter Mansfield of the University of Nottingham were awarded the 2003 Nobel Prize in Physiology or Medicine for their “discoveries concerning magnetic resonance imaging“. The Nobel citation acknowledged Lauterbur’s insight of using magnetic field gradients to determine spatial localization, a discovery that allowed rapid acquisition of 2D images. Mansfield was credited with introducing the mathematical formalism and developing techniques for efficient gradient utilization and fast imaging. The actual research that won the prize was done almost 30 years before while Paul Lauterbur was a professor in the Department of Chemistry at Stony Brook University in New York.

ONCOLOGY

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Association Between Use of a Scalp Cooling Device and Alopecia After Chemotherapy for Breast Cancer

 

Chemotherapy-induced alopecia is a common and distressing adverse effect. In previous studies of scalp cooling to prevent chemotherapy-induced alopecia, conclusions have been limited. As a result, a study published in JAMA (2017;317(6):606-614), was performed to evaluate whether use of a scalp cooling system is associated with a lower amount of hair loss among women receiving specific chemotherapy regimens for early-stage breast cancer and to assess related changes in quality of life.

 

The investigation was a prospective cohort study conducted at 5 US medical centers of women with stage I or II breast cancer receiving adjuvant or neoadjuvant chemotherapy regimens excluding sequential or combination anthracycline and taxane (106 patients in the scalp cooling group and 16 in the control group; 14 matched by both age and chemotherapy regimen). The study was conducted between August 2013 and October 2014 with ongoing annual follow-up for 5 years. Scalp cooling was initiated 30 minutes prior to each chemotherapy cycle, with scalp temperature maintained at 3oC (37oF) throughout chemotherapy and for 90 minutes to 120 minutes afterward. The main outcome measures were self-estimated hair loss using the Dean scale assessed 4 weeks after the last dose of chemotherapy by unblinded patient review of 5 photographs. A Dean scale score of 0 to 2 (<50% hair loss) was defined as treatment success. A positive association between scalp cooling and reduced risk of hair loss would be demonstrated if 50% or more of patients in the scalp cooling group achieved treatment success, with the lower bound of the 95% CI greater than 40% of the success proportion. Quality of life was assessed at baseline, at the start of the last chemotherapy cycle, and 1 month later. Median follow-up was 29.5 months.

 

Results showed that among the 122 treated patients, the mean age was 53 years (range, 28-77 years); 77.0% were white, 9.0% were black, and 10.7% were Asian; and the mean duration of chemotherapy was 2.3 months (median, 2.1 months). No participants in the scalp cooling group received anthracyclines. Hair loss of 50% or less (Dean score of 0-2) was seen in 67 of 101 patients (66.3%) evaluable for alopecia in the scalp cooling group vs 0 of 16 patients (0%) in the control group (P<0.001). Three of 5 quality-of-life measures were significantly better 1 month after the end of chemotherapy in the scalp cooling group. Of patients who underwent scalp cooling, 27.3% reported feeling less physically attractive compared with 56.3% of patients in the control group (P=0.02). Of the 106 patients in the scalp cooling group, 4 (3.8%) experienced the adverse event of mild headache and 3 (2.8%) discontinued scalp cooling due to feeling cold.

 

According to the authors, among women undergoing non-anthracycline-based adjuvant chemotherapy for early-stage breast cancer, the use of scalp cooling vs no scalp cooling was associated with less hair loss at 4 weeks after the last dose of chemotherapy. The authors added that further research is needed to assess outcomes after patients receive anthracycline regimens, longer-term measures of alopecia, and adverse effects.

International Study Suggests Nodding Syndrome Caused By Response To Parasitic Protein

 

Nodding syndrome is a form of epilepsy that occurs in children between the ages of 5 and 16 who live in distinct regions of Tanzania, Uganda and the Republic of South Sudan. It is characterized by head nodding, seizures, severe cognitive deterioration and stunted growth. Nodding syndrome may lead to malnutrition and patients have died through seizure-associated traumas such as fatal burns and drowning. Many studies have reported an association between Nodding syndrome and Onchocerca volvulus, a parasitic worm that can also cause river blindness. The worm is spread by black flies in specific geographic areas, where clusters of Nodding syndrome have been observed. However, it was unclear whether the worm caused this neurological disorder. However, just recently, according to an article published in Science Translational Medicine (15 February 2017), scientists at the National Institutes of Health (NIH) have uncovered new clues to the link between Nodding syndrome Onchocerca volvulus. The study, suggests that the mysterious neurological disease may be caused by an autoimmune response to the parasitic proteins.

 

For the study, the authors compared serum samples from patients with Nodding syndrome and healthy controls who all lived in the same village in Uganda. The results showed high levels of antibodies to leiomodin-1 in the samples obtained from patients. In addition, antibody to leiomodin-1 was also present in cerebrospinal fluid of patients with Nodding syndrome. Previous studies have shown leiomodin-1 is found in muscles, but this was the first time it was seen in the nervous system. To confirm the finding, the authors also examined brain tissue and found leiomodin-1 inside brain cells, notably in regions associated with symptoms of Nodding syndrome. Furthermore, when healthy neurons, in vitro, were treated with serum from the patients and antibodies against leiomodin-1, they did not survive, but removing the antibodies increased brain cell survival.

 

The results of this study suggest that Nodding syndrome may be an autoimmune disease, in which the immune system incorrectly attacks the body’s own proteins. According to the authors, the immune system creates antibodies to fight off the parasite following infection with Onchocerca volvulus. However, those antibodies also bind to leiomodin-1, so the immune system – incorrectly – will attack brain cells that contain that protein, which can result in symptoms of Nodding syndrome. The authors added that the findings also suggest that therapies targeting the immune system may be effective treatments against the disorder and possibly other forms of epilepsy. “And yes, similar to the mosquitos the carrying malaria and other parasites, exterminating black flies and getting rid of the parasite should stop the disorder from occurring.

 

More research is needed to learn about the role of leiomodin-1 in healthy people as well as in individuals with epilepsy. For example, one-third of controls also had leiomodin-1 antibodies, but it is unclear whether these individuals may eventually develop Nodding syndrome.

 

For more information:

<https://www.ninds.nih.gov/Disorders/All-Disorders/Epilepsy-Information-Page>

<https://neuroscience.nih.gov/ninds/Home.aspx>

<https://directorsblog.nih.gov/2014/06/03/from-uganda-to-nih-to-solve-a-seizure-mystery/>

FDA Approves Siliq to Treat Psoriasis

 

Psoriasis is a skin condition that causes patches of skin redness and flaking. Psoriasis is an autoimmune disorder that occurs more commonly in patients with a family history of the disease, and most often begins in people between the ages of 15 and 35. The most common form of psoriasis is plaque psoriasis, in which patients develop thick, red skin with flaky, silver-white scales.

 

The FDA has approved Siliq (brodalumab) to treat adults with moderate-to-severe plaque psoriasis. Siliq’s active ingredient (brodalumab) binds to a protein that causes inflammation, inhibiting the inflammatory response that plays a role in the development of plaque psoriasis. The drug is intended for patients who are candidates for systemic therapy (treatment using substances that travel through the bloodstream, after being taken by mouth or injected) or phototherapy (ultraviolet light treatment), and have failed to respond, or have stopped responding to other systemic therapies.

 

Siliq’s safety and efficacy were established in three randomized, placebo-controlled clinical trials with a total of 4,373 adult participants with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. More patients treated with Siliq compared to placebo had skin that was clear or almost clear, as assessed by scoring of the extent, nature and severity of psoriatic changes of the skin.

 

Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with Siliq during clinical trials. Siliq users with a history of suicidality or depression had an increased incidence of suicidal ideation and behavior compared to users without this history. A causal association between treatment with Siliq and increased risk of suicidal ideation and behavior has not been established. Because of the observed risk of suicidal ideation and behavior, the labeling for Siliq includes a Boxed Warning and the drug is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Siliq REMS Program. Notable requirements of the Siliq REMS Program include the following:

 

Prescribers must be certified with the program and counsel patients about this risk. Patients with new or worsening symptoms of depression or suicidality should be referred to a mental health professional, as appropriate.

Patients must sign a Patient-Prescriber Agreement Form and be made aware of the need to seek medical attention should they experience new or worsening suicidal thoughts or behavior, feelings of depression, anxiety or other mood changes.

Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive Siliq.

 

Siliq is also approved with a Medication Guide to inform patients of the risk of suicidal ideation and behavior, and that because Siliq is a medication that affects the immune system, patients may have a greater risk of getting an infection, or an allergic or autoimmune condition. Patients with Crohn’s disease should not use Siliq. Health care providers should also evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Siliq. Health care providers should not administer Siliq to patients with active TB infection, and should avoid immunizations with live vaccines in patients being treated with Siliq.

 

The most common adverse reactions reported with the use of Siliq include joint pain (arthralgia), headache, fatigue, diarrhea, throat pain (oropharyngeal pain), nausea, muscle pain (myalgia), injection site reactions, influenza, low white blood cell count (neutropenia) and fungal (tinea) infections. Siliq is marketed by Bridgewater, New Jersey-based Valeant Pharmaceuticals.

Curried Shrimp Rissoles Topped with Mango

For months, I have been trying to come up with a new shrimp recipe, good enough to share with everyone. Finally, here it is. Versatile enough to serve as an entr?e or an appetizer. There were enough made, so that we ate them for two dinners; plus, Jules could snack on them over the long weekend. BTW, Jules gives this recipe a 5. He’s eating them hot or cold, I like them best warm with hot gravy spooned over and chopped fresh mango scattered over the top, and a garnish of fresh cilantro. ©Joyce Hays, Target Health Inc.

Ingredients

 

For the dough:

 

2 cups almond flour

1 3/4 cups and 2 1/2 Tablespoons boiling water (for the dough)

1 Tablespoon extra virgin olive oil

Salt (to taste)

1 eggs

Panko

Canola oil (or extra virgin olive oil) for frying

 

For the filling:

 

2 pounds medium to large shrimp, cleaned and de-veined

1 onion, chopped very well

10 fresh garlic cloves, chopped

3 stalks scallion, well chopped up to half the white section

1 cup sweet corn kernels (fresh or frozen)

1 cup mango chutney

Pinch black pepper

Pinch pink Himalayan salt

1 teaspoon ground nutmeg

1 teaspoon curry powder

1 Tablespoon white or brown sesame seeds, toasted

1/2 Tablespoon almond flour

1 Tablespoon butter

1 bunch fresh Parsley, very well chopped

1 onion to cook the shrimp

 

Gather all the ingredients in one place. ©Joyce Hays, Target Health Inc.

 

Directions

 

Get all of the ingredients out

Do all chopping, slicing, cutting, etc.

 

Chopping parsley. ©Joyce Hays, Target Health Inc.

 

Chopping garlic, onion, mango. ©Joyce Hays, Target Health Inc.

 

For the dough:

 

1. Pour the water into a saucepan and bring it to a boil over high heat. To the water, add the butter and the salt. When starts boiling, reduce to low heat and add the flour. Stir constantly with a wooden spoon until the dough forms a compact ball.

 

2. Turn off the heat, place the dough on a table and allow to cool to room temperature. Knead the dough with your hands, make one large ball and set aside.

 

The dough should look like this. ©Joyce Hays, Target Health Inc.

 

Gravy

 

Make your favorite seafood gravy that’s light, or no gravy at all. I put together a simple sour cream, flour, teaspoon extra virgin olive oil, curry, garlic, chopped mushrooms in a saucepan, then set aside.

 

You don’t need gravy for this recipe but I made a simple gravy, to see if the recipe needed it and it doesn’t. © Joyce Hays, Target Health Inc.

 

 

For the filling:

 

1. In a skillet, with extra virgin olive oil and a little chicken stock or broth, and the parsley, cook the chopped onion until it’s golden.

 

Cooking onion, garlic, parsley. ©Joyce Hays, Target Health Inc.

 

 

2. Place the shrimp in the skillet with the onion/parsley. While stirring constantly, cook the shrimp for about 2 or 3 minutes.

 

Add the shrimp to the parsley mixture and cook for about 2 minutes, stirring all the time, to get both sides of the shrimp cooked. When shrimp are done, remove quickly into a bowl and cook more, until all the shrimp are done. ©Joyce Hays, Target Health Inc.

 

After cooked and oil drained on paper towel, put shrimp in bowl to be chopped.

©Joyce Hays, Target Health Inc.

 

 

3. Chop by hand, the shrimp garlic and the bunch of parsley. Don’t chop too much. You want the filling to have texture to it. You want small pieces of the shrimp to show when the little rissole is cut open to eat.

 

4. To the chopped shrimp add the curry powder, nutmeg, all seasonings, all spices, all herbs, corn kernels, chopped mango and mix to combine well.

 

Here is the filling. I need to chop some of the big pieces of shrimp some more and then the filling will be ready to become part of the dough. ©Joyce Hays, Target Health Inc.

 

 

Make the Rissoles

 

1. Roll out the dough with a rolling pin.

2. Cut small circles by using a coffee mug, turned upside down

 

3. Place portions of the filling in the center of each circle. Put another circle over the filling and press the edges of the two circles, together to seal. Crimp the edges with a fork.

 

Fry the rissoles

 

1. In a bowl, whisk the eggs with a fork.

2. Put Panko on a flat plate

3. Dip the rissoles in the beaten egg and then cover them with the Panko.

 

The beaten eggs to dip the rissoles in before frying. ©Joyce Hays, Target Health Inc.

 

The Panko to roll both sides of the rissoles after dipping in the beaten egg, just

before frying.  ©Joyce Hays, Target Health Inc.

 

4. Heat the oil in skillet. When the oil is hot, add the rissoles and fry them on both sides until golden on each side.

 

5. Once they are fried, place them on a plate with paper towel.

 

6. Then put the rissoles on a serving platter. Add some gravy, if you wish. Scatter chopped mango over the top and garnish with chopped cilantro.

7. Put some chutney on the table to serve with the shrimp rissoles.

 

Platter of curried shrimp rissoles, ready to serve. ©Joyce Hays, Target Health Inc.

 

Over the rissoles, gravy added, plus scattered chopped mango over the top of the rissoles.

©Joyce Hays, Target Health Inc.

 

These curried shrimp rissoles are so delicious, you can’t stop eating them.

©Joyce Hays, Target Health Inc.

 

We ate these all weekend. Mmmmmm outstanding! ©Joyce Hays, Target Health Inc.

 

These rissoles were the entre, with which a simple salad was served.

©Joyce Hays, Target Health Inc.

 

Wonderful with mango chutney ! ©Joyce Hays, Target Health Inc.

 

Chilled Prosecco was perfect with the Shrimp Rissoles. ©Joyce Hays, Target Health Inc.

 

This was the perfect long weekend for us. The outstanding event was attending the MetOpera’s, I Puritani, shining gem of outstanding bel canto, with brilliant voices, lyrics, conductor. On our list of perfect operas, this is tied at the top.

 

All Bravas and Bravos, standing ovations, were well deserved. If you can still get tickets for this glorious opera, there are three more performances in February; try not to miss this superlative production by the great master, Vincenzo Bellini.

 

The electrifying Frech coloratura, Diana Damrau is Elvira, gripped by madness and love; great Mexican tenor, Javier Camarena, a sensation in his recent appearances in other bel canto works, takes on the role of her beloved and heroic Arturo. If you think you hear a little Verdi, you would be almost right.

 

Bellini, earlier composer, had a great influence on Guiseppe Verdi, not the other way around. Bellini wrote long swaths of melody, a style that influenced all of Europe’s composers including Chopin and yes, Wagner. I would venture to say that IMO, Wagner’s greatest creation, Tristan and Isolde, was influenced by Vincenzo Bellini.

 

Click the link for my favorite aria from Bellini’s, I Puritani, sung by the greatest tenor who ever lived, Luciano Pavarotti

 

Vincenzo Bellini, operatic genius, makes LGBT proud

 

 

We were so enthralled by this glorious opera, that at dinner afterwards, the first thing we ordered was, two Bellinis, toasting the genius of Vincenzo Bellini. Opera doesn’t get any better than this production of, I Puritani.

 

From Our Table to Yours !

 

Bon Appetit!

 

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