Advancing the Science

Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.

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19 hours ago · Researchers look at possible link between low vitamin B12 and Parkinson's symptoms

An elderly woman sitting outside with her son and grandchildren

By Jay Furst

Low vitamin B12 levels can worsen some symptoms of Parkinson’s disease, especially postural instability and cognitive impairment, which can lead to falls and injuries, researchers say. Lower vitamin B12 levels also are associated with higher Hoehn-Yahr stage, the tool for assessing disease severity, and neuropathy in Parkinson’s patients.

While it’s not clear why, there may be a relationship between vitamin B12 and acetylcholine, a neurochemical that’s believed to be a key to cognition and postural control. The neurons that make and use acetylcholine die during the course of the disease, says Mayo Clinic neurologist Rodolfo Savica, M.D., and one theory is that vitamin B12 deficiency may exacerbate that process.

Also relevant is that carbidopa/levodopa, the most commonly prescribed medication for Parkinson’s, can reduce vitamin B12 levels, especially at high dosage, which is common later in the disease course as more medication is needed to manage tremor or slow movement.

“Currently, we do not have very effective therapies for these symptoms in Parkinson’s disease, as they do not respond well to levodopa,” says Stuart McCarter, M.D., a Mayo Clinic neurology resident who worked with Dr. Savica and colleagues at Mayo Clinic and the University of Minnesota on a recent study of vitamin B12 and Parkinson’s.

The study, which was published in Mayo Clinic Proceedings in May, investigates the potential link between low vitamin B12, acetylcholine-related brain function, and disease severity. The study proposes that supplementing vitamin B12 could be helpful to improve cholinergic transmission and potentially motor and cognitive function.

Falls
and the injuries that result are among the difficulties that face Parkinson’s
patients. Among the characteristics of the disease is freezing of gait — a
sudden inability to start or continue walking, especially when the person is
changing directions or may be distracted, and contributes to fall risk. Cholinergic
dysfunction may play a role in freezing of gait, and recent clinical trials
suggest that anticholinesterase inhibitors, which increase acetylcholine, may decrease
falls in Parkinson’s disease.

“Cognitive
impairment with Parkinson’s is multifactorial and is likely to be related to a
combination of underlying issues,” Dr. McCarter says. They include
microvascular disease, Lewy body deposition, beta-amyloid plaques and tau
neurofibrillary tangles, and dysfunction of multiple neurotransmitters. “Acetylcholine
is just one part of the complex neuronal dysfunction that’s associated with
cognitive impairment. But there’s evidence that it plays an important
role.”

Dr.
Savica also says it’s unlikely to be a “straightforward linear causal
process” between vitamin B12 deficiency and cholinergic dysfunction, but
it merits investigation. Among the challenges for researchers is that vitamin
B12 is commonly measured as a total serum level, which lacks sensitivity and
can be insufficient in measuring accurate B12 status, and seemingly normal lab
values may not reflect vitamin B12 status in the brain.

Dr.
Savica, who has more than 15 years of clinical as well as research experience in
Parkinson’s disease and related disorders, says he hopes the study in
Proceedings will raise awareness about the potential importance of vitamin B12
status.

“It
may not be well-known in the non-neurology setting that high doses of levodopa
can decrease vitamin B12 levels, which in some cases leads to peripheral
neuropathy and also worsen balance,” he says.

Vitamin B12 levels should be checked in patients with Parkinson’s disease and supplemented if low, he says. In Mayo’s movement disorders practice, it’s common to start patients who are on levodopa with a vitamin B12 supplement. “This is usually a combination pill with small amounts of vitamin B6 and folate,” he says.

The
cutoff for vitamin B12 deficiency varies between testing laboratories but is
typically less than 200ng/L in the blood. However, given the inaccuracy of
serum vitamin B12, impairment of vitamin B12-mediated function likely occurs at
levels higher than 200 ng/L. Methylmalonic acid is another value that providers
use to help determine severity of vitamin B12 deficiency and is more
representative of true status.

Combination
pills typically contain about 2.5mg of folate, 25mg of vitamin B6, and 1mg of
vitamin B12, although there is no standardized recommendation of the amount of
each vitamin required for beneficial effects. Important to note is that too
much vitamin B6 can be toxic to the nervous system, so patients should exercise
caution with vitamin B6 supplementation.

“The
goal of vitamin supplementation currently is to avoid the complications induced
by levodopa,” Dr. McCarter says, especially when the patient is on high
dosage and presenting with symptoms such as numbness and tingling in the hands
and feet. “However, our study hopes to provide an additional rationale for the
role of vitamin B12 in Parkinson’s disease.”

Next steps: Mayo Clinic researchers are working on a retrospective study to look for a connection between vitamin B12 deficiency and postural instability and cognitive impairment. They plan to complete this study by the end of 2019.

Watch the video about this study from Mayo Clinic Proceedings below.

2 days ago · Mayo Clinic study explores cumulative radiation from CT use

By Jay Furst

Computed tomography (CT), which uses specialized X-rays to create images of areas inside the body, has revolutionized medicine in the nearly 50 years since it became commonly available. From kidney stones to cancer, CT has become an indispensable diagnostic tool.

In 1980, an estimated 3 million CT scans were made in the U.S. By 2007, the estimated total was closer to
60 million, and by 2015 the estimate was 80 million. A CT scan combines a
series of X-rays from different angles to create cross-sectional images that
can be used to discover illness or injury, guide surgery and treatment plans,
and monitor outcomes.

Despite its common use, the exposure of patients to ionizing radiation from CT is incompletely understood, says Konrad Stopsack, M.D., formerly a Mayo Clinic internist who now is at Memorial Sloan Kettering Cancer Center in New York City. For that reason, he and James Cerhan, M.D., Ph.D., chair of Mayo Clinic’s Department of Health Sciences Research, initiated a retrospective study on the cumulative doses of ionizing radiation from CT that patients in Olmsted County received over a 10-year period.

“We wanted to learn more about exposure to ionizing radiation from CT among adults, as well as which parts of the population were most affected, and for what clinical indications CTs were obtained,” says Dr. Stopsack, lead author of the study, which is posted online at the Mayo Clinic Proceedings website and will be published in the journal’s October issue. “Previous studies have looked at these questions but either were unable to track people over a long period of time or only looked at those patients who repeatedly came back to the same hospital, so were not necessarily representative of the general population.”

The study was made possible by using the resources of the Rochester Epidemiology Project, the vast treasure trove of medical records that have been logged in Rochester and Olmsted County since 1966, and it could not have been done as efficiently elsewhere, says Dr. Cerhan, an epidemiologist and the Ralph S. and Beverley Caulkins Professor of Cancer Research at Mayo Clinic.

“The Rochester Epidemiology Project allows the combination of access to detailed clinical data over a long period of time on a geographically defined population,” he says.

Dr. Stopsack, who graduated from Mayo Clinic’s Internal Medicine Residency Program in 2017 and conducted the research with Dr. Cerhan while still at Mayo, says the study reviewed all CT examinations performed in Olmsted County from 2004 to 2013. Mayo Clinic, Olmsted Medical Center and affiliated hospitals perform CT scans, and the institutional review boards of the two institutions approved the study.

Today Konrad Stopsack, M.D., is a research associate in the Philip Kantoff Lab at Memorial Sloan Kettering Cancer Center.

“The number of people who end up getting a
CT scan is pretty impressive,” Dr. Stopsack says. “Half the
population we sampled received a CT within 10 years. That’s quite a lot.”

Of the 54,447 adults whose de-identified medical
records were examined, almost half — 26,377 — underwent at least one CT. The
total number of CTs performed was 107,961 during the 10-year period, with the
largest group (44.2 percent) of patients having 2-4 CTs during that period.

The study relied on administrative claims data
to determine which CTs people had and then to calculate the radiation dosage
the patient received.

“We found quite striking differences in
radiation dosage,” Dr. Stopsack says. “Patients who were older or had
very low or very high body mass index, for example, received higher radiation
doses over time.” Also factors were education and race; educational levels
both lower and higher than four-year college degrees were associated with
higher doses, and African-Americans received higher doses than whites.

“The association of age, smoking and perhaps body mass index with CT is not very surprising, even if most of that had not been described previously in research,” says Dr. Stopsack. “However, it is quite striking that people with lower educational attainment and African-Americans accumulated higher doses.”

Dr. Stopsack believes that this disparity may reflect poorer health on average across these specific groups.

Of 600 CTs among 200 patients who had accumulated high doses over one decade, 70 percent were for restaging or assessing the extent of cancerous tumors and lymphoma, abdominal pain, infection, kidney stones, follow-up of (potentially cancerous) nodules or masses, and to check for pulmonary embolism.

“That’s another striking number,” Dr. Stopsack says. “Two percent of the population sampled received really high estimates doses over 10 years, in excess of 100 millisieverts (measurement of radiation exposure).”

In terms of potential implications for
clinical care, Dr. Stopsack says the high cumulative doses potentially could be
reduced if CTs were ordered for a shorter list of indications, or if lower
doses were exam were used.

“Replacing CT with ultrasound in patients
who may have kidney stones, for example, is one area that has been successfully
studied in a randomized trial,” he says. “Another is follow-up CTs
for lymphoma patients. Our results underline that CTs for these patients are
relatively big contributors to cumulative radiation.”

Other dose-reduction strategies noted in the
study are decreasing doses per exam and more generally, addressing variations
in dose between institutions.

Most important, though, is the value of CT to
diagnose illness and and treat patients, the researchers say.

“When a CT is clinically indicated, the benefit is almost always greater than any potential harms, including from radiation,” Dr. Stopsack says.

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Related resources:

Tue, Jun 18 6:00am · Research and innovation thrive at Mayo and beyond, with an assist from Mayo Clinic Ventures

Mayo Clinic Ventures commercializes technologies to benefit patients while generating revenue to support clinical practice, research and education. Thanks in part to licensing and partnership efforts, 2018 was a banner year for Mayo Clinic Ventures’ financial performance.

By Kate Stober

Mayo Clinic has a long and storied history of firsts — the first nonprofit practice aligned with research and education, the discovery of cortisone, the first hip replacement approved by the Food and Drug Administration. The list goes on. When patients need answers, Mayo staff aim to find solutions.

Many of these innovations often have far-reaching effects, changing the delivery of health care on a much larger scale. When it comes to translating discoveries into products that help patients, that’s where Mayo Clinic Ventures comes in.

Mayo Clinic Ventures commercializes Mayo Clinic discoveries to benefit patients around the world while generating revenue to support clinical practice, research and education.

Andrew Danielsen

“We take the innovation and discoveries from the Research, Education and Practice shields, and help translate them into products that can help patients,” says Andrew Danielsen, chair of Mayo Clinic Ventures. Danielsen leads a diverse team of skilled professionals working with Mayo Clinic staff to advance medical care.

All ideas welcome

Mayo Clinic Ventures receives over 700 ideas per year, about one-third of which move forward into some form of development. Although researchers and physicians are the most active staff in terms of creating new discoveries, Danielsen says ideas come from staff across the organization.

Allied health staff have played key roles in developing biopharmaceutical drugs, diagnostic tests and algorithms to improve medical imaging, all of which Mayo Clinic Ventures has licensed to outside companies.

“We sometimes hear, ‘Well, if I’m not a Ph.D. or an M.D., I shouldn’t be inventing.’ That’s not at all true,” Danielsen says.

Staff whose ideas are seen as having potential for commercialization can get seed funding to further develop their concept. They also can take advantage of the external industry connections and the product development experience of Mayo Clinic Ventures staff.

Many Mayo Clinic products are on the market today, helping millions of patients. Examples include Cologuard, an at-home colon cancer screening test that was first offered at Mayo Clinic in 2014; HF10, an implantable device designed to reduce back and leg pain; and individualized medicine screening tools used at Myriad Genetics Inc., a genetic testing company.

A banner year for innovation

Thanks in part to licensing and partnership efforts, 2018 was a banner year for Mayo Clinic Venture’s financial performance.

In 2018, Mayo Clinic Ventures activities contributed 5% of Mayo Clinic’s net income.

It’s exciting, but not exactly surprising.

“Four out of the last six years, we’ve had record years in terms of revenue and net income. This year is also off to a very strong start, and we are hopeful for yet another record year,” Danielsen says. “It’s a testament to the creativity and passion that Mayo Clinic staff have for innovation and improving care options for our patients.”

Danielsen says that taking an active approach has driven increased revenues. The Mayo Clinic Ventures team prides itself on reaching out to potential business partners and providing specialized support to Mayo Clinic staff interested in advancing a new technology.

“We really encourage folks to reach out and talk to us about any of their ideas or discoveries,” Danielsen says. “We can help guide them through the process, and provide financial and other support.”

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Thu, Jun 13 6:00am · How spinal stimulation research is working to restore function after paralysis

Left: Peter Grahn, Ph.D., and Megan Gill, D.P.T.. Right: Megan Gill, D.P.T., (seated) assists
Jered Chinnock as part of a clinical trial to determine if spinal cord circuitry can be modulated with electrical stimulation and rehabilitation to restore function lost to paralysis.

Mayo Clinic has challenged its researchers to transform the practice of medicine with research that leverages multidisciplinary expertise, technology and therapeutic advances to address unmet clinical needs. This story describes how one team has risen to the challenge, elevated the level of teamwork across disciplines and achieved novel results using spinal stimulation to enable function after spinal cord injury. The story focuses on two team members — both alumni of Mayo Clinic College of Medicine and Science schools in different disciplines.


The two first authors on a recent publication in Nature Medicine have personal connections to the groundbreaking research they reported in the manuscript. Peter Grahn, Ph.D., a senior engineer in the Department of Neurologic Surgery and alumnus of Mayo Clinic Graduate School of Biomedical Sciences; and Megan Gill, D.P.T.,, an alumna of Mayo Clinic School of Health Sciences who also has a doctorate in physical therapy, have worked on a team of researchers from Mayo Clinic, UCLA and Houston Methodist during the last four years. The team has studied an emerging research approach to restore function in people with paralysis due to spinal cord injury. From a personal perspective, Drs. Gill and Grahn have each had a health-related event that affected their mobility

The study

In 2014, a team of 15 Mayo Clinic scientists and clinicians from neuro-engineering, neurosurgery, and physical medicine and rehabilitation acquired internal funding to collaborate with V. Reggie Edgerton, Ph.D., of UCLA, to establish his team’s spinal neuromodulation approach at Mayo Clinic. The approach was developed in conjunction with Susan Harkema, Ph.D., from the University of Louisville. Building on Dr. Edgerton’s work, the Mayo team designed the clinical trial protocol and acquired Mayo Clinic Institutional Review Board approval and an Investigational Device Exemption from the Food and Drug Administration (FDA). Mayo Clinic received FDA permission to use an electrical stimulation device for research purposes to study a condition not covered by its approved label. Co-principal investigators were Kendall Lee, M.D., Ph.D., Department of Neurologic Surgery and director of Mayo Clinic’s Neural Engineering Laboratories; and Kristin Zhao, Ph.D., Department of Physical Medicine and Rehabilitation and director of Mayo Clinic’s Assistive and Restorative Technology Laboratory.

The Mayo Clinic team’s objective was to determine whether spinal cord circuitry could be modulated with electrical stimulation and rehabilitation to restore function lost to paralysis. Two patients with complete spinal cord injury were enrolled in the trial.

“Dr. Edgerton’s team showed us the ropes of how to program the epidural electrical stimulator so we could replicate what they’d achieved in their studies,” says Dr. Grahn. “During our initial programming session, the subject moved his leg using his own intent. When we observed this ability, everyone in the room gasped.”

The Mayo team replicated the UCLA team’s results within the first week of the study and continued to see what more they could achieve. They accomplished much more than basic leg movements.

Jered Chinnock, who injured his spinal cord at the thoracic vertebrae in the middle of his back in a snowmobile accident in 2013, was the first participant in the Mayo Clinic study. He had complete loss of function and feeling below the middle of his torso. Dr. Lee and his neurosurgery team had implanted an electrode array in the epidural space at a specific location below Chinnock’s injury. The electrodes were connected to a pulse generator that was implanted near the patient’s abdomen. The generator communicates wirelessly to an external controller.

Chinnock participated in 113 rehabilitation sessions in the lab over 43 weeks in 2016 and 2017. Team members programmed the stimulator and recorded electrophysiology and biomechanical data. Dr. Gill led the physical therapy team and provided expertise about how rehabilitation with the device should occur. They provided Chinnock with physical assistance and used a body-weight harness to help him stand and step. With electrical stimulation, he was able to stand, swing his legs and shift his weight to maintain his balance. Because he didn’t regain sensation in his legs, Chinnock initially used mirrors to view his leg movement while rehabilitation team members provided verbal and tactile cues to describe his leg position, movement and balance.

“ Seeing our research subjects’ accomplishments is exciting, We’re grateful for their phenomenal effort and contributions to our research.”

Peter Grahn, Ph.D.

The results

By the end of the study, Chinnock no longer needed a harness and had only occasional help from the therapists. He learned to use his body to transfer weight, maintain balance, and propel forward on a treadmill while using his arms on the support bars to help with balance. He required minimal verbal cues and periodic glances at his legs. He progressed to using a front-wheeled walker to step with minimal assistance from the team.

“I was surprised by the amount of motor activity Jered was able to do with stimulation,” says Dr. Grahn. “Looking at past studies, we thought he may be able to stand without assistance and move his legs while lying down. No studies had shown that someone with complete paralysis could stand and take steps. With the stimulator off, the subject remains completely paralyzed below the level of his injury. These findings suggest that even the most severe cases of paralysis likely have some connections intact across the injury, and that neural networks below the spinal cord injury can be facilitated by epidural stimulation to restore functions such as standing and stepping. Altogether, these results support the concept that task-specific rehabilitation performed during spinal stimulation can enable functional reorganization of the spinal cord to recover functions lost due to spinal cord injury.”

Dr. Grahn says the results generated by the Mayo team could be attributed to factors such as the patient’s specific injury, some aspect of the rehabilitation or key changes made to stimulator settings. Certainly, their findings have sparked more questions to investigate.

The team is endeavoring to further explore the use of epidural electrical stimulation and other emerging spinal neuromodulation techniques, combined with intense physical therapy, to help paralyzed patients regain function. A subsequent trial will help answer some of the unknowns from the first — to gain a better understanding of how and why the epidural electrical stimulation enables these functional gains and which patients will respond to stimulation.

Now that Chinnock is home in Tomah, Wisconsin, he works on an exercise program the Mayo team specified. He has approval to use the device for standing with a walker and to improve his trunk strength and balance during daily activities in his wheelchair.

The personal connection

While it can’t be measured as part of the data, Dr.Gill and Dr. Grahn say their personal experiences had a significant impact on their perspectives and dedication to the project.

At age 18, Dr. Gill developed a systemic infection that required a year of rehabilitation and healing to allow normal use of her left leg. That experience led her to pursue a medical career and develop personal drive to help patients achieve their goals.

Megan Gill, seated, adjusts red harness straps.
Megan Gill, D.P.T., adjusts paralysis study harness straps.

Dr. Grahn has had quadriplegia due to spinal cord injury since 2005 and uses a powered wheelchair for mobility. When he was 18, he dove off of a dock in central Minnesota and hit the shallow bottom of a lake, fracturing the fifth vertebrae in his neck. He was instantly paralyzed and spent almost a year in rehabilitation.

Dr. Grahn, whose injury has affected his motor functions more than the patient in the Mayo Clinic study, says he felt a strong sense of excitement as Chinnock’s abilities progressed during the study. “In the early stages of my own recovery, I admit there was a sense of jealousy when someone in the rehab gym with a similar prognosis as mine would recover to walk again. My point of view is different now. For the first couple of months after my accident, I thought if I worked hard enough at rehabilitation, I’d get better as I had with past sports-related injuries. Over time I realized my disability was permanent, and I experienced dark times during that period in my life. Eventually I realized that life is full of challenges, and learning to live with my disability was one of those challenges. I was also curious why the spinal cord doesn’t heal.

Peter Grahn, Ph.D., poses sitting with Anthony Windebank, M.D.; Luis Lujan, Ph.D.; and Kendall Lee, M.D., Ph.D.
Peter Grahn, Ph.D., poses with Anthony Windebank, M.D.; Luis Lujan, Ph.D.; and Kendall Lee, M.D., Ph.D.

“Fast forward 13 years, and I’m in a unique position to contribute to making discoveries and generating information to advance the research fields of neuromodulation and spinal cord injury. It was exciting to see the potential of what our patient could do when we turned on the stimulator. Our work demonstrates that spinal cord injury severity is more of a spectrum. We may be able to improve function even in severely injured patients who are diagnosed with the worst category of injury.”

Dr. Gill says Dr. Grahn advocated for epidural stimulation research at Mayo Clinic. “Peter is a prime example of someone living to their greatest capacity. Never has his disability held him back. He has gained a deep understanding of the neuromodulation literature and has developed the skills to communicate this information to all team members regardless of the level of expertise in paralysis research. And, because he has a spinal cord injury, he has unique understanding of our research subjects’ situation.”

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Wed, Jun 12 6:00am · Mayo Clinic researchers dig deeper to map brain tumors

Drs. Tatum (left) and Quinones-Hinojosa using brain mapping during a procedure.

Surgeons
in the operating room must achieve a delicate balance when removing a brain
tumor: eradicate as much of the cancer as possible, and avoid injury to parts
of the brain responsible for motor control, speech, and more.

For
years, doctors have been using brain mapping – that is, stimulating the brain
with electrodes to create a map of various brain functions – to identify ideal
areas for tumor removal. While traditional brain-mapping methods have been
crucial to reducing post-surgical deficits and improving patient quality of
life, key challenges remain. For example, current electrostimulation techniques
record the activity of the gray matter near the surface of the brain (the
cortex) while less is known about activity in the white matter below it (the
subcortex). Both the cortex and subcortex contain areas important to brain
function.

New work being done at Mayo Clinic’s Florida campus aims to look deeper. A multidisciplinary team of investigators including William Tatum, D.O., Kaisorn Chaichana, M.D., Alfredo Quinones-Hinojosa, M.D., and colleagues is looking at innovative ways to collect data from the hard-to-read white matter. The researchers’ most recent focus is on glioma, a common type of brain cancer that can be aggressive. “Surgeries to remove glioma generally involve white matter, but this has been tricky to map,” says Dr. Tatum. “We think our updated technologies will help us see the connections beneath the surface of the brain.”

The
researchers are working to determine whether new electrostimulation devices
with a deeper reach can be used to better define which parts of the subcortex
are most essential to important functions, reducing the risk of adverse
outcomes.

Accurate
white-matter mapping would also allow surgeons to remove a larger proportion of
primary brain tumors including gliomas. “The extent of resection would have a
direct effect on life expectancy,” Dr. Tatum says. “And with more than 12,000 new
patients diagnosed with glioblastoma (the most aggressive type of glioma)
annually, that’s a big deal.”

“In the past, standard commercially available electrodes have been available in a very restricted repertoire, in linear strips or grids placed on the brain,” says Mayo neurologist and project collaborator Anthony Ritaccio, M.D. “My Mayo colleagues have developed new electrode arrangements that are ingenious and ergonomic, but also so basic and practical that you wonder why no one has thought of them before.”

New
electrostimulation devices are just part of the brain-mapping innovations
underway at Mayo. Dr. Ritaccio and colleagues are also looking at ways to
improve how brain activity recordings are interpreted. “We’re learning that passive
recordings of brain activity can lead to a remarkably better understanding of
areas of the brain responsible for tasks like listening and speech,” he says.
For instance, researchers are finding that they can record brain signals of a
person reading aloud, and decode the data to create speech from a prosthetic
voice. “Our current work will be able to utilize Mayo’s new advancements in brain
mapping to create a superior environment for understanding our
electrostimulation data,” says Dr. Ritaccio.

“Electrostimulation
has been used for the last half century, and it’s always had its benefits and
drawbacks,” he continues. “We’re working together at Mayo to make it better,
faster, and safer for patients.”

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Thu, Jun 6 6:00am · Not all stones are created equal

image of different kidney stones next to a penny and a marble, which are approximately the same size

Mayo Clinic’s CT Clinical Innovation Center recently released the first-ever quantitative Stone Analysis Software (qSAS) for characterizing renal stones from CT images. The product is available at no charge for research use through a software sharing agreement.

Cynthia McCollough, Ph.D., Division of Medical Physics, Department of Radiology at Mayo Clinic in Rochester, co-director of Mayo’s CT Clinical Innovation Center and the Brooks-Hollern Professor, says the new software measures the entire volume, shape and size of a renal stone. “A marble and a penny might have a similar diameter at the center, but they’re shaped very differently. Existing standard-of-care technology would not do a good job at describing the differences between stones like these two objects.”

Dr. McCollough says accurate quantification of renal stones is rarely included in a radiology report. “The standard of care is to take a CT scan, draw a line across the stone in one image, use a measurement tool to quantify the diameter, and compare the value to past and future values for the same stone. Hand-drawn measurements aren’t a good way to measure or make decisions because a round stone and an irregularly shaped oblong stone could appear to be the same at the center, yet they represent very different stone burdens to the patient. Qualifiers such as small and big don’t tell the complete picture.

“A stone that’s smooth like a pebble on a beach might pass through the body relatively easily. A rough, spiky stone may be more likely to get stuck in the ureter, be too difficult to pass and require surgery. We can spare the patient the attempt to pass a stone such as that and go directly to surgery.”

The qSAS characterizes every image of the stone, giving its length, width, height, volume, mineral type and roughness. With this higher standard of measurement, physicians can be confident about a stone’s growth from one exam to a subsequent one, according to Dr. McCollough.

Andrea Ferrero, Ph.D., and Cynthia McCullough, Ph.D.

The software, which has been in development at Mayo Clinic for about a decade and has been used to support Mayo researchers, generates fully standardized stone reports in less than five minutes. The only user interaction required is a coarse delineation of the kidneys. After that, the software automatically identifies any renal stones and excludes hardware in the kidneys such as stents and nephrostomy tubes.

Funding for the project was provided by the National Institute of Diabetes and Digestive Diseases as part of Mayo’s O’Brien Urology Research Center (John Lieske, M.D., principal investigator).

Behind the scenes

Ongoing development in the lab is focused on determining how easy it will be to break up a stone based on what is measured in the CT image. Andrea Ferrero, Ph.D., a recent graduate of the Department of Radiology’s Diagnostic Medical Physicist Residency Program, has been a key driver in preparing the software for release and developing new capabilities such as measuring stone fragility.

“Without Andrea and research technologist Jayse Weaver, we would never have been able to package our various software tools into a comprehensive, user-friendly software product,” says Dr. McCollough. “There is tremendous interest in this software from the renal stone research community.”

Researchers interested in the software can visit the CT Clinical Innovation Center at Mayo Clinic to see how the qSAS works: https://ctcicblog.mayo.edu/ hubcap/qsas-stone-toolkit/.

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Mon, Jun 3 6:00am · Hear from the experts on hereditary amyloidosis

Amyloidosis is a rare disease that occurs when a substance called amyloid builds up in your organs. Amyloid is an abnormal protein that is produced in your bone marrow and can be deposited in any tissue or organ.

Hereditary amyloidosis (familial amyloidosis) is an inherited disorder that often affects the liver, nerves, heart and kidneys. Many different types of gene abnormalities present at birth are associated with an increased risk of amyloid disease. The type and location of an amyloid gene abnormality can affect the risk of certain complications, the age at which symptoms first appear, and the way the disease progresses over time.

Dr. Dyck (left), with (continuing right) moderator John L. Berk, M.D., Boston University School of Medicine, Akshay Desai, M.D., Brigham and Women’s Hospital, Michael Polydefkis, M.D., Johns Hopkins Hospital.

Recently NeurologyLive featured Mayo Clinic neurologist P. James B. Dyck, M.D., and three other experts in a “Peer Exchange” panel discussing hereditary amyloidosis.

In the 14 video segments in Understanding Hereditary ATTR (hATTR) Amyloidosis and the Recent Advances in Management, Dr. Dyck and his peers walk viewers through the current knowledge of hereditary amyloidosis, treatments and ongoing research.

According to the Amyloidosis Foundation, in the U.S., each year about 4,500 people are newly diagnosed with the most common type of amyloidosis. Much fewer are diagnosed with hereditary amyloidosis, making this a very rare variation of what is already a rare disease.

At Mayo Clinic, research drives everything we do for patients. In the case of amyloidosis, several leading experts oversee research programs including:

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Mon, May 20 6:00am · Leading and learning in neurological research

The brain, lit up artistically in blue light

Mayo
shares neurological research and advancements at AAN meeting

Among more than 15,000 attendees at the 2019 American Academy of Neurology (AAN) Annual
Meeting
in Philadelphia, May 4-10, Mayo Clinic had a strong presence. Mayo scientists and clinicians
led 38 courses and gave 84 lectures at the world’s largest gathering of
neurologists. Nearly 60 Mayo speakers shared key research findings and clinical
best practices across a wide range of seminars, plenary and poster sessions, platform
presentations, skills workshops, and leadership and experiential learning
programs.

In addition, several Mayo neurologists
were recognized with prestigious honors:

Claudia Lucchinetti receives an award
At the 2019 American Academy of Neurology Annual Meeting in Philadelphia, AAN president Ralph Sacco, M.D., right, presented a sculpture to Mayo Clinic neurologist Claudia Lucchinetti, M.D., in honor of her Robert Wartenberg Lecture on multiple sclerosis. This lifetime achievement lecture is awarded to a neurologist for excellence in clinically relevant research and is presented during the Presidential Plenary Session at the annual meeting.
Photo courtesy of the American Academy of Neurology.

“It’s impressive to see the breadth of
Mayo Clinic’s involvement across the American Academy of Neurology,” says Claudia Lucchinetti, M.D., the Eugene and Marcia
Applebaum Professor of Neurosciences, and chair, Department of Neurology. “Neurologists from all Mayo Clinic campuses directed and/or participated in numerous educational
courses, as well as presented their latest clinical and basic science research,
which included collaborations with many other Mayo departments and disciplines.

“Altogether, Mayo Clinic continues to have
a significant impact on the Academy across education, research and practice. The
annual meeting is a remarkable illustration of the work not only of our faculty,
but also of our neurology residents and fellows. In addition, many Mayo
neurologists are in leadership roles within the Academy, with broad
representation on many major committees, subcommittees, sections and leadership
development programs.”

Plenary presentations

AAN shines a spotlight on the most significant advances in the research and treatment of neurological diseases during the annual meeting’s plenary sessions, including two led by Mayo Clinic.

Progress in Understanding Progressive MS: From the Microscope to the Bedside

Dr.
Lucchinetti received the 2019 Robert Wartenberg Lecture Award, given annually
to a neurologist for excellence in clinically relevant research. At the
presidential plenary session on May 5, she delivered the Robert Wartenberg
Lecture, conveying how detailed neuropathological assessment and evaluation of multiple
sclerosis lesions from different stages and phases of the disease may help
better inform some of the underlying factors that drive progression in MS.

“Treatment that prevents or substantially slows progression in MS remains one of our greatest unmet needs,” says Dr. Lucchinetti. “Through this lecture, I had the opportunity to share what we can learn from microscopic analysis of MS tissues, and how this work translates to the development of novel biomarkers, correlates with MRI imaging parameters, and may lead to the discovery of new treatments that more specifically target the pathogenic mechanisms that drive irreversible progression in MS. It was an honor to highlight not only the research from my own lab in collaboration with my colleagues in the U.S., Canada and Europe, but also present important advances made by my Mayo Clinic colleagues from the Division of MS and Autoimmune Neurology.”

A Placebo-Controlled Study of Galcanezumab in Patients with Episodic Cluster Headache: Results from the 8-week Double-blind Treatment Phase

David Dodick speaks at the Academy of Neurology Annual Meeting in Philadelphia
Mayo Clinic neurologist David Dodick, M.D., presented a Clinical Trials Plenary Session on a study of galcanezumab in patients with episodic cluster headache at the 2019 American Academy of Neurology Annual Meeting in Philadelphia.
Photo courtesy of the American Academy of Neurology.

In
the clinical trials plenary session, David Dodick, M.D., presented on
the efficacy and safety of galcanezumab to prevent episodic cluster headache. The
study showed a significant reduction in the frequency of cluster headache
attacks within the three weeks after the administration of the drug. These
results are particularly relevant, as there currently are no drugs approved by
the Food and Drug Administration to prevent cluster headache.

“Based
on our study, the FDA has fast-tracked review of galcanezumab for the
prevention of cluster headache, indicating the significant unmet treatment need
in patients suffering from this relatively uncommon but incredibly disabling
disorder. It was an honor to present our work and be part of the palpable,
meaningful presence Mayo Clinic has at this important event,” Dr. Dodick says.

Depth
and breadth of research

Mayo Clinic research presented at the AAN
meeting represented a variety of specialties and areas of study. For example:

  • Angelman syndrome: Children with Angelman Syndrome often have trouble falling asleep and
    sleeping through the night. A new study
    suggests those difficulties may be reduced when patients receive iron
    supplementation therapy.

  • Autoimmune inflammatory disorders: The drug eculizumab significantly reduced the risk of
    relapse with neuromyelitis optica spectrum disorder, a rare but severe
    autoimmune inflammatory disorder. Mayo Clinic researchers and
    international collaborators reported their findings, which also were published
    in the New England Journal of Medicine

  • Brain tumors: Patients
    with brain tumors often suffer from drug-resistant seizures. Researchers have
    discovered that genetic mutations are more important in originating seizures
    than tumor grade, location or pathology. These findings may
    help design therapies for patients.

  • Cognitive aging: “Brain reserve” protects against cognitive aging, according to
    Mayo Clinic findings.
    Even in midlife, general health factors like smoking, vascular disease and
    depression may lower that reserve, affecting brain health and risk for
    dementia.

  • Multiple sclerosis: Some people with MS feel squeezing, called the “MS hug,” in the chest
    or abdomen. A new study finds
    a majority of patients who report the “hug” had symptoms from another cause,
    including heart attack, pulmonary embolism and shingles.

  • Parkinson’s disease: A new study
    suggests salivary gland biopsies on both sides of the jaw are safe for patients
    with Parkinson’s Disease and may be useful in monitoring disease progression
    and treatment.

  • Sleep apnea:
    People who stop breathing during sleep may have higher accumulations of the
    toxic protein tau, a biological hallmark of Alzheimer’s disease, in the part of
    the brain that manages memory, navigation and perception of time, according to
    a preliminary study.

  • Transient global amnesia: Transient global amnesia is a sudden inability to
    form new memories, typically lasting four to six hours. New research
    suggests recurrence may be associated with earlier age of onset and personal
    and family history of migraine.

Awards
and Honors

Other Mayo Clinic representatives
received honors at AAN, including leadership appointments and awards.

  • Diego Z. Carvalho, M.D., received the Wayne A. Hening Sleep Medicine Investigator Award.
  • Lyell K. Jones, Jr., M.D., was approved by AAN voting members to serve on the AAN Institute Board of Directors.
  • Bryan Neth, M.D., Ph.D., received the Consortium of Neurology Residents and Fellows Essay Contest Award.
  • Vijay Ramanan, M.D., Ph.D., earned the Enhanced Resident Leadership Program Award.

AAN Leadership Programs

AAN Committee Members

AAN Annual Meeting Committee

The
American Brain Foundation is AAN’s foundation to bring researchers and donors
together to cure brain diseases and disorders. Mayo representation includes:

Board of Directors

Research Advisory Committee

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