The WCC Note

Your Weekly Guide to Harmonizing Clinical Trial Imaging

Posts Tagged ‘functional MRI’

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.

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Posted in Brain, Cancer, Nanoparticles, Neuro | No Comments »

fMRI: Speech, Imaging Angiogenesis, and MRI: Leukemia – Vol. 2, Number 27

Wednesday, December 3rd, 2008

fMRI: SPEECH

Speech Content and Speaker Identification Reflected in Functional Brain MR Images
Attempts to create machines capabile of recognizing human speech commenced in the 1950s, yet the human brain’s ability to understand speech and identify its speaker has proved a profoundly complex and nuanced higher-order function, difficult to mechanically replicate.  Untangling the threads of this intricate process has progressed recently, as researchers examined listeners’ brain auditory cortexes and used neural “fingerprints” to decipher what, and to whom, the subjects were listening.  Researchers from the University of Maastricht, Netherlands, used imaging combined with multivariate statistical pattern recognition of speech sounds to examine the brains’ receptive speech pathways.  Initially, seven participants listened to the speech sounds of three Dutch vowels from three Dutch speakers.  The distinct brain activation patterns underwent scrutiny with high-resolution functional MR imaging (fMRI), the sounds evoking responses in the superior temporal cortexes of the subjects.  As reported in Science, the researchers subsequently expanded on their work by using functional MRI brain images and their response patterns to decode sounds and their speakers.

Conclusion:  Early work by Dutch researchers has deciphered speech content and speaker identification using functional MRI imaging.

IMAGING ANGIOGENESIS

Imaging the Many Faces of Tumor Angiogenesis
The National Cancer Institute describes tumor angiogenesis as a proliferating blood vessel network that penetrates malignant tumors to provide oxygen and nutrients and remove wastes.  Creation of this neovascularity requires molecules released from the tumor cells, and without these molecular signals and their resultant new vessel formation, the cancers cannot progress.

These molecular investigators cause a cascade of events, initially activating host tissue genes that subsequently incite proteins to be produced, which then initiate the new vessels to grow.  The presence of this increased blood flow produces a local environmental change that can be perceived by dynamic contrast-enhanced imaging.

Conclusion:  In this and upcoming issues of The WCC Note, studies will be profiled to illustrate examples in which current and developing imaging techniques capture and exploit angiogenesis, a fundamental biological feature of cancer.

MRI: LEUKEMIA

MRI of Angiogenesis in Leukemia Portends Decreased Chemotherapy Response
A cancer of the blood cells, leukemia strikes blood-forming tissue such as bone marrow, sending an abnormal number of cells into the blood stream.  In the United States, an estimated 44,270 new cases will be diagnosed in 2008.

A recent study in the journal Blood examined dynamic contrast MRI in patients with acute myeloid leukemia (AML) and correlated it with their outcomes.  The authors, from National Taiwan University Hospital in Taipei, prospectively imaged 78 patients with AML at diagnosis and after induction chemotherapy.  Bone-marrow angiogenesis assessment consisted of three factors: peak enhancement ratio (reflecting tissue perfusion), amplitude (denoting vascularity), and volume transfer constant (indicative of vascular permeability).

The results showed peak and amplitude findings decreased significantly with remission.  Those individuals presenting with higher peak or amplitude values exhibited shorter disease-free and overall survival.  Along with old age and unfavorable karyotype, higher peak value at diagnosis independently predicted overall survival.

Conclusion:  Authors reporting a study in Blood showed that heightened bone-marrow angiogenesis on MRI in leukemia patients predicted adverse outcomes.  They suggest the information may help profile which individuals could benefit from anti-angiogenic therapy.

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Posted in Brain, Oncology | No Comments »

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.

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Posted in Eye, General Education, Neuro | No Comments »

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.

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Posted in Eye, Neuro | No Comments »

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.

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Posted in Brain, Neuro | No Comments »