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Archive for the ‘Neuro’ Category

fMRI: Brain, Imaging Angiogenesis, and Nano-Particles/Cancer – Vol. 2, Number 28

Thursday, December 11th, 2008

fMRI: BRAIN

MRI Helps Translate Thought Into Sound for Man with “Locked-In Syndrome”
When Jean-Dominique Bauby wrote his stunning and transcendent memoir, The Diving Bell and the Butterfly, he communicated it letter by letter by blinking his left eye.  Bauby suffered from “locked-in syndrome,” a rare neurological disorder that paralyzes all voluntary muscles except those controlling eye movements.

For such patients, no means of communication exist except nonvocal ones.  However, a recent article describes an advance which could someday allow these individuals to communicate through sound instead of gestures.  Naturenews reports a study that used an implanted brain electrode to permit a man with locked-in syndrome to create vowel sounds, after using functional brain MRI to assess his speech.

Scientists from Boston University placed the electrode in the speech area of the man’s brain and a computer decoded the brain signals.  The electrode activated a speech synthesizer that accurately replicated three vowel sounds.  As reported at the Society for Neuroscience’s annual meeting in November 2008, the team will subsequently work on computer decoding of consonants to allow the creation of complete words.  Naturenews notes that functional MRI or electrodes placed on the skull could also be used to decode brain speech.

Conclusion:  A man with locked-in syndrome was able to create audible vowel sounds using an implanted brain electrode and speech synthesizer, after having his thoughts analyzed by functional MRI.

IMAGING ANGIOGENESIS

Exploiting Novel Molecules That Create and Comprise Cancer Vessels
The new blood vessels that grow and sustain cancer originate when stimulated to occur by molecules released from cancer cells.  These molecular activators of angiogenesis include a host of proteins and small molecules.  The study of these factors may bring to fruition new and robust imaging for tumor detection and surveillance, as well as innovative therapeutic modalities for tumor cure.  The two molecules thought to be the most important sustainers of tumor growth are vascular endothelial factor (VEGF) and basic fibroblast growth factor (bFGF).  Other activators of angiogenesis include prostaglandins E1 and E2, nicotinamide, and interleukin 8, among others.  The resultant new tumor vessels display their own molecules, providing more investigative avenues to target.  The following article highlights one recent attempt to exploit these molecular features of cancer.

NANO-PARTICLES/CANCER

Imaged Nanoparticles Target Cancer Vessels and Decrease Tumor Size
Integrin ανβ3 comprises one factor found on some tumor vascularity.  Researchers at University of California, San Diego created a nanoparticle targeted at integrin that was linked with the chemotherapeutic agent doxorubicin.  The authors made it fluorescent and injected it into a live mouse pancreatic cancer model.  As reported in Proceedings of the National Academy of Science, the authors noted modest decreased primary tumor growth, but significant reduction in the draining lymph-node metastases.  Featured in Naturenews, the study also reported that the treatment reduced metastases in a mouse kidney cancer model.

Conclusion:  Fluorescent nanoparticles, linked with a chemotherapeutic agent, that were targeted at molecules found exclusively on new vessels have been reported to decrease metastases in mice pancreatic and kidney cancers.

fMRI Economics, Digital Imaging Innovation, and NIH Leadership – Vol. 2, Number 25

Monday, October 20th, 2008

fMRI ECONOMICS

Neurophysiology of Economic Behavior at Auctions Studied with Functional MRI
Peoples’ behavior in economic markets has been evaluated mathematically using game theory, for which the Nobel Prize in economics was awarded in 1994.  Game theory postulates that the bids made by buyers reach an equilibrium (the “Nash equilibrium”) when no player can improve his or her her payoff by changing strategy, give the strategies of the other bidders.  However, bidders have a propensity to bid above this equilibrium amount, called “overbidding.”  The burgeoning field of neuroeconomics offers an alternative methodology, that of neurophysiology, to analyze factors influencing human economic motivators.  A recent study in Science examined the phenomenon of people overbidding at auctions by using functional MRI (fMRI).  The lead author from Rutgers University reported that 17 participants underwent a series of bidding experiments and their brain fMRI blood-oxygen levels and behavior were studied.  The results showed lower blood-oxygen levels in the striatum when bidders lose an auction, but not when they win.  The authors propose that the fear of losing in a social situation, not the joy of winning, explains auction overbidding.

Conclusion:  People’s economic behavior can be studied using neurophysiology.  Functional MRI and behavioral experiments support the theory that the fear of losing a social competition, not the joy of winning, leads people to overbid at auctions.

DIGITAL IMAGING INNOVATION

Innovative Curved Imaging Device Simulates the Human Eye
Digital and video cameras employ flat image-recording surfaces.  While their resolution can display more than 10 million pixels, a bright and distortion-free image proves problematic with flat imagers.  To avoid distortion at lens edges a combination of lenses are used, but these have proved heavy and costly, and yield dark images.  In contrast, animal eyes consist of curved surfaces allowing a wide filed of view and lower aberration.  Recently, researchers at the University of Illinois and Northwestern University created a novel electronic-eye camera that uses silicon electronics that are compressible and stretchable.  The mechanics allow molding into a hemispherical shape resembling the human eye.  According to an article published in Nature, the optics depend on two innovations.  First, thin metallic wires interconnect semiconductor photodetectors on a silicon wafer, allowing elastic compressibility despite high strain.  Second, elastomeric elements can transform the initial planar configuration into the hemispherical geometry.  These achievements could portend a broad array of applications, including new medical imaging systems.

Conclusion:  Technical innovations herald the advent of digital imaging systems shaped like the human eye.

NIH LEADERSHIP

Renowned Radiologist Dr. Elias Zerhouni Leaving NIH Directorship This Month
It was an epic day in radiology back in 2002, when one of our ranks ascended to the loftiest of roles in United States medicine.  Named Director of the U.S. National Institutes of Health (NIH), Dr. Elias Zerhouni took charge of the country’s flagship medical institution, which now has more than 18,000 employees and an annual budget of $29.5 billion.  His elevation proved a signal event in the continuing incorporation of radiology into the crux of modern medicine. The nation entrusted its massive infrastructure of medical research and patient care to his stewardship and, under his deft guidance, the supertanker of the U.S. healthcare system sailed forward.

Some of Dr. Zerhouni’s accomplishments include creating the “NIH Roadmap,” a compelling list of NIH initiatives that would make a profound difference in biomedical research.  He also established interdisciplinary programs to tackle major public health problems, such as the NIH Strategic Plan for Obesity Research and the Neuroscience Blueprint. In addition, Zerhouni launched the Clinical and Translational Science Awards, the first systematic change of approach to clinical research at the NIH in 50 years. Also under his leadership, The Molecular Libraries program developed small molecule screening centers and PubChem provided free access to discoveries about the chemistry and biology of small molecules.

Zerhouni’s agency supported high-risk/high-impact research and funding of early-career investigators. During his tenure, the Human Microbiome Project was launched to study the collective genomes of all microorganisms present in or on the human body, a largely unexplored territory.  The NIH invested in studying epigenomics, the processes regulating how and when genes are turned on and off, and funded creating a comprehensive gallery of three-dimensional shapes of body proteins. He increased public access to health-related publications, accelerating release of manuscripts from NIH-supported research, and put forth effort to make the incomparable NIH resources accessible to the public. His predecessor praised Dr. Zerhouni’s excellent relations with Congress and noted that he stood up to the President on stem-cell research.

The mission of the NIH encompasses pursuit of fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to extend healthy life, reducing the burdens of illness and disability. Dr. Zerhouni’s departure takes place at the end of October.

Conclusion: Dr. Elias A. Zerhouni, a radiologist with MRI expertise, has announced his imminent departure as Director of the U.S. National Institutes of Health.

MRI: Schizophrenia & Eyes and Phase Microscopy: Malaria – Vol. 2, Number 24

Friday, September 26th, 2008

PHASE MICROSCOPY: MALARIA

Imaging Membranes of Red Blood Cells Offers New Insights into Malaria
Cell membranes provide barriers between living cells and their external environments.  Biomembrane receptors, channels, signals, and scaffolding maintain cellular growth, metabolism, and homeostasis.  The role of membranes encompasses findings important in the broader array of human disease, including infection and neoplasm.  For example, abnormal cell-cell adhesion participates in tumor progression.  In addition, membrane proteins can be exploited as targets in drug development.  A recent, eloquent study from teh Massachusetts Institute of Technology reported noninvasive optical techniques to assess membranes of cells infected with malaria.  The authors used tomographic phase microscopy and diffraction phase microscopy to image red blood cell membranes.  Malaria leads to structural, biochemical and mechanical changes in host red blood cells and, as reported in Proceedings of the National Academy of Sciences, the techniques created three-dimensional refractive index maps showing nanoscale cell-membrane fluctuations.

Conclusion:  Recent imaging of red blood cell membranes shows their fluctuations in malaria, and promises a potentially powerful means to identify the cell-membrane dynamics occurring in disease.

MRI: SCHIZOPHRENIA

Functional MRI Findings in Unaffected Relatives of People with Schizophrenia
Schizophrenia affects approximately 1.1% of U.S. adults, usually presenting in the late teens or early twenties in men, and in the twenties and thirties in women.  Rarely, children are afflicted.  Hallucinations, delusions, cognitive defects, and disordered thinking characterize the disease.  Since, when performing tasks, patients exhibit dysfunction in the anterior cingulated cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) and their unaffected relatives can display poor cognitive control, researchers used functional MRI to study patients’ relatives.  As reported in Neuropsychopharmacology, researchers led by the University of Missouri-Columbia evaluated 17 unaffected relatives of schizophrenic patients and 17 healthy controls.  The functional MRI of the relatives demonstrated decreased activity in the DLPFC when performing a color-naming task (the “Stroop task”), but showed normal activity in the ACC.  The Stroop task measures selective attention and is widely used to study attention deficits in schizophrenic people.  The study concluded that the genetic risk for schizophrenia may be associated with DLPFC dysfunction, while the ACC dysfunction in schizophrenic patients may be related to abnormalities intrinsic to the disease.

Conclusion:  Unaffected relatives of schizophrenia patients can show functional brain MRI changes in the prefrontal cortex.

MRI: EYES

High-Resolution MR Improves Eye Imaging
A number of MRI scanners currently use microscopy coils for imaging fingers and toes.  To image the orbit and eye, most MRI scanners utilize standard head coils.  As reported in the journal Eye, researchers headed by the University of Leeds (UK) employed a microscopy surface coil in a commercially-available MRI scanner to obtain high-resolution images of the eye and orbit.  The researchers stated that the images depticted structures not previously observed and clearly showed the pathology present.

Conclusion:  High-resolution MRI coils could revolutionize orbital imaging.

MRI: Alzheimer’s, OCD & Spine – Vol. 2, Number 23

Tuesday, September 16th, 2008

MRI: ALZHEIMER’S

Brain MRI Temporoparietal Measurements in Prodromal Alzheimer’s Disease
The National Institute for Aging estimates that up to 4.5 million Americans suffer from Alzheimer’s disease.  To assess the early imaging appearance of the disease, researchers in a multicenter prospective trial led by Boston University followed the brain MRI measurements of various anatomic brain locations over time and correlated them with metal status.  As reported in Neurology, 16 brain regions of interest underwent MRI scrutiny in 66 subjects.  The people who developed Alzheimer’s disease over the course of the study displayed greater atrophy rates in six brain areas, compared to those individuals who showed stable, mild cognitive impairment throughout the study.  These areas included the hippocampus, entorhinal cortex, temporal lobe, middle temporal gyrus, fusiform gyrus, and inferior temporal gyrus.  Those subjects who advanced to Alzheimer’s disease over the time frame demonstrated differentially greater rates of atrophy, compared to normal cognitive controls in five of these areas and in the inferior parietal lobe.  Correlation occurred between the rate of mental status change and rates of atrophy in these areas.

Conclusion:  Brain MRI exams in podromal Alzheimer’s disease show differential rates of atrophy in the temporoparietal regions that correlate with cognitive decline, and carry potential for use as markers in early Alzheimer’s disease.

MRI: OCD

Obsessive-Compulsive Disorder Patients and Their Close Relatives Displayed Functional MRI Signs
Obsessive-compulsive disorder (OCD) is an anxiety disorder described by the National Institute of Mental Health (NIMH) as recurrent, unwanted thoughts and/ore repetitive behaviors.  The number of affected American adults age 18 or over approaches 2.2 million, representing roughly 1 percent of people in this age range per year.  Symptoms frequently commence in childhood or adolescence, with a mean age of 19.  The condition displays a familial link, though studies to investigate the inheritance pattern, thought to be complex and involving multiple genes, have been ongoing in the U.S.  In light of this complicated genetic puzzle, researchers at the University of Cambridge (England) sought to identify alternative disease markers using functional brain MRI.  The study examined 14 patients with OCD, 12 of their unaffected first-degree relatives, and 15 unaffected matched controls.  The participants underwent visual tasks to elicit different components of behavioral flexibility.  A recent report in Science examines their findings, reporting abnormally decreased activation in several cortical regions, including the lateral orbito-frontal cortex, in OCD patients and their unaffected close relatives.  The authors conclude that such brain-based markers may provide powerful assistance in solving the genetic basis of the disorder.

Conclusion:  Functional brain MRI demonstrated markers for obsessive compulsive disorder.

MRI: SPINAL CORD

First Spinal Cord Genetic Atlas Released
The National Spinal Cord Injury Statistical Center (NSCISC) estimates that as of 2007, approximately 255,702 people in the United States were living with spinal cord injuries.  The current widely available imaging methods for such individuals can display their macroscopic cord findings.  Such findings reflect the cord’s anatomy and histology, the foundation of which ultimately occurs at the molecular level.  The more refined imaging can become, the further it can delve into the microscopic cellular and subcellular milieu.  As reported in Nature News, an ambitious project to map the expression patterns of 18,500 genes in the mouse spinal cord has released data on the first 2,000 of these genes.  Ultimately, the Allen Institute for Brain Science plans to release the Allen Spinal Cord Atlas, created from 20-micrometer thick sections at millimeter intervals.  The journal explains that pictures will be “resolvable down to one micrometer per pixel of screen – individual nerve cells are upwards of 10 micrometers in diameter.

Conclusion:  A new atlas of mouse spinal cord genetic expression holds promise as a reference f0r normal anatomy, with detail never heretofore accomplished.

MRI: Catheter Guidance & Stroke and HGF: Emphysema – Vol. 2, Number 21

Tuesday, August 12th, 2008

MRI: CATHETER GUIDANCE

In Vivo Real-Time MRI Catheter Guidance Proves Feasible
In the setting of heart rhythm dysfunction, it is sometimes necessary to map out, assess, and treat the electrical pathways in the heart.  Electrophysiological studies of the heart achieve this and entail directing catheters to specific locations within the heart.  Currently, physicians employ conventional fluoroscopy to guide the catheters.  However, MRI affords superior soft-tissue visualization compared to fluoroscopy and lacks fluoroscopy’s radiation.  Thus it would be advantageous to place catheters under MRI guidance, rather than the conventionally used fluoroscopy.  Potential barriers to electrophysiological studies are the magnetic force and electromagnetic interference inherent in MRI.  Reporting in Circulation, researchers at Johns Hopkins University achieved successful intracardiac positioning of catheters in dogs, and performed electrograms and pacing with the catheters.  No evidence of thermal injury occurred.  Subsequently, the researchers achieved two human real-time, MRI-guided catheter mapping studies.

Conclusion: Real-time, MRI-guided electrophysiology studies prove feasible – and afford better soft-tissue visualization and lack radiation compared to conventional fluoroscopy.

HGF: EMPHYSEMA

Intranasal HGF Reverses Lung Emphysema in Mice
Chronic respiratory disease is the fourth leading cause of death in the United States and 4.1 million adults have been diagnosed with emphysema.  Hepatocyte growth factor (HGF) affects multiple factors, including stem cells, epithelial proliferation, and wound healing.  A recent study from Japan evaluated the intranasal administration of HGF on mine with elastase-induced emphysema.  The HGF inhalation occurred twice a week for one to four weeks.  Published in Molecular Therapy, the results revealed significant amelioration of airspace enlargement and alveolar destruction.  Within two weeks, elevated static lung compliance returned to control levels.  The authors report: “… intranasal treatment with HGF reverses both the physiological and morphometric changes of lung emphysema, possibly through stem-cell mobilization and alveolar regeneration.”

Conclusion:  Intranasal human growth factor reverses induced emphysema in mice.

MRI: STROKE

Imaging of In Vivo Single Neurons Shows Cells Take on New Roles After Stroke
Stroke ranks third (behind heart disease and cancer) as a leading U.S. cause of death, killing 150,074 people in 2004 alone.  The process of stroke recovery is thought to be accomplished by living brain cells assuming the tasks of injured ones.  To assess whether single neurons perform new functions at the expense of their original ones, versus acquiring multiple roles, researchers at the University of British Columbia performed in vivo two-photon calcium imaging.  Using an adult mice role model, neurons and glia were studied over two eight weeks after ischemic damage.  As published in the Journal of Neuroscience, the single-cell calcium imaging showed that surviving neurons that normally process information for a single contralateral limb instead processed information for multiple limbs.  This peaked at one month after injury; at two months neurons became more selective for a preferred limb.

Conclusion:  Imaging of in vivo single neurons after stroke shows surviving cells initially process information for multiple new sites, then become more selective.