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Archive for the ‘General Education’ Category

2009: Looking Back and Looking Ahead in Imaging – Vol. 3, Number 11

Thursday, December 31st, 2009

Last summer while reviewing literature for this newsletter, I spent an afternoon on a porch elevated alongside an Idaho road.  While mountains made a diaphanous blanket of color in the distance, and breezes prickled through tree leaves that flickered and shuffled like molecules in entropy, it occurred to me that our understanding of disease processes, due to our ability to image them, has altered fundamentally since I entered radiology 20 years ago.  Rather like a J.D. Salinger’s Glass family member, I felt a kind of epiphany, as silly as that sounds, sitting in a lawn chair among the plants withering in the mountain heat.  And yet, it is this kind of realization about our profession – that it does not and will not stand still – that makes us so lucky to be a part of it.

As the panorama of molecular, in vivo cellular, and micro environmental imaging spreads before us, along with a continuing stream of new technologies that fire out of laboratories with so many endless possibilities, it is our great fortune to work in a profession that allows us, at its core, to serve as fly wheels of steady utility as diagnosticians and also play a role in medical innovations that are occurring today and that will continue to do so for years to come.

This year’s final issue of The WCC Note veers away from the mainstream of practiced radiology and takes us down less-traveled roads toward some experimental imaging highlights of 2009.  From Dr. Pomeranz and myself, we wish you very happy holidays and a joyous and healthy new year.

- Margaret D. Phillips and Stephen J. Pomeranz

ACCOLADES FOR IMAGING ADVANCES

In 2008, the Nobel Prize in Chemistry Went for the Discovery of Green Fluorescent Protein, Which Revolutionized the Imaging of Small Structures, Allowing In Vivo Cellular Imaging.  What Major Accolades Were Bestowed for Imaging This Year?

  1. Once again, a Nobel Prize went to imaging – this time for techniques that allow digital imaging and electronic communications, such as this newsletter.  These discoveries ultimately revolutionized the practice of radiology.
    a.  In 2009, the Nobel committee awarded the Physics prize for inventing an imaging semiconductor circuit, the charge-coupled device (CCD), and for developments in optical fibers that allowed communications based on transmission of light.
    b.  The prize went to two U.S. researchers, Willard S. Boyle and George E. Smith, from Bell Laboratories in Murray Hill, NJ, as well as Charles K. Kao of the United Kingdom and Hong Kong, China.
    c.  The charge-coupled device came to fruition from a desire to create a memory storage device, and it originated after a 1.5-hour discussion between Drs. Boyle and Smith one afternoon in 1969.  It relied on the photoelectric effect discovered by Einstein, for which Einstein himself won the Nobel Prize in 1921.  Attempting to make advances toward a picture phone, Boyle and Smith imagined arrays of photocells that would emit electrons in proportion to the intensity of incoming light.  The electrons in the photocells would then be read and thereby make an image – changing an optical image to a digital one.
    d.  In an online interview, Drs. Boyle and Smith were asked what set apart Bell Laboratories, which has received seven Nobel Prizes.  Their answers were freedom, intelligent management that allows pursuit of interests, an institution financially well positioned to afford appropriate equipment, and excellent people – allowing fellowship and interchange of ideas.
    e.  Dr. Kao used ultra-pure glass fibers to transmit light in 1966.  Since the frequency of light waves is so much greater than electrical waves, transmission is much faster than with copper cables and radio waves.
  2. The Japan Prize from the Science and Technology Foundation of Japan went to radiologist David Kuhl, M.D. from the University of Michigan.  His work in the 1950s developed radionuclide emission tomography that led to, among other areas, PET scanning.

NEW DIRECTIONS IN IMAGING

What Were Some Experimental or Progressive Techniques Published in 2009 That Reflect New Directions or Hold Promise for the Future?

  1. The in vivo tracking of cells with MRI has undergone clinical study outside the United States using superparamagnetic iron oxide particles.
  2. Imaging atoms within an organic molecule absorbed on a surface was performed with scanning tunneling microscopy.
  3. Breast-specific gamma imaging with a high-resolution gamma camera was reported to show 93 percent sensitivity in 28 biopsy-proved known lobular carcinomas, in a retrospective multicenter study.
  4. Molecular imaging of the breast underwent review with description of, among others, the gene array analysis of tumors, phenotypic imaged tumor differences, MR tumor spectroscopy, and fluorescent probe imaging.
  5. Atherosclerotic plaque was imaged in vivo at the molecular levels by using the MR contrast agent P947 that targets matrix metalloproteinases in plaque.
  6. Using infared imaging guidance, researchers caused subtotal ablation of mice tumors, which resulted in T-cell immune responses and tumor regression.
  7. Minimally invasive autopsy to detect cause of death as an alternative to conventional autopsy was reported to show 93 percent of overall findings and 94 percent of major findings.  The technique used whole-body CT, MR, and ultrasound-guided 12-gauge needle biopsy of the heart, both lungs, liver, both kidneys, and spleen.
  8. Apoptotic (early cell death) processes underwent time-lapse imaging in live cells.  Researchers used a polarity-sensitive biosensor with switchable fluorescence states that allowed only the apoptotic cells to be detected.
  9. Reporter gene imaging of human mesenchymal stem cells implanted in porcine myocardium was performed with PET-CT.
  10. A single atom could be imaged by detecting electrons emerging from its surface using an aberration-corrected electron microscope.

CONCLUSION

The year 2009 saw Nobel Prizes awarded for techniques that ultimately brought about digital imaging and filmless teleradiology, the Japan Prize given for radioisotope tomography leading to PET; and a myriad of experimental imaging science that increasingly refined and exploited visualization of small structures – down to the atomic level.

Research and reporting by Margaret D. Phillips, M.D.
Reviewer and publisher:  Stephen J. Pomeranz, M.D.

For full sources and credit, please download the PDF copy of the newsletter here

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Micro-Imaging Advances
Vol. 3, Number 1

Wednesday, January 14th, 2009

SCANNING THE HORIZON

We at WorldCare Clinical send you best wishes for a happy new year!  In a departure from our regular format, this issue begins 2009 with a turn away from currently applied advances in medical imaging.  Like a telescope surveying the landscape of the future, however near or far off it may be, this issue profiles experimental and theoretical studies in which imaging is – or could be – of importance.
– Stephen J. Pomeranz, M.D., and Margaret D. Phillips, M.D., Contributing Editors

MICRO-IMAGING ADVANCES

From the Scientific Locomotive, Some Bullets Fired into the Future
The macroscopic features depicted on current radiological imaging studies reflect processes occurring at the cellular, and ultimately, the molecular and micro-environmental levels.  In this light, a number of more recent developments may ultimately influence the way we perceive and perform medical imaging – and may link some imaging techniques with disease interventions.

We begin the year by turning our lens toward the horizon.  The following studies, briefly profiled, serve as a sampling of the past year’s innovative literature.  They depict the depth and promise of newer scientific paths that may gain increasing currency in the years to come.

Molecular and Microscopic Imaging
The year 2008 saw the Nobel Prize in Chemistry awarded for the discovery of and research on a green fluorescent protein (GFP) in jellyfish, a finding which ultimately changed the scale on which imaging could be done.  This advance opened a door into the world of the minute – a path to structures of unprecedented small scale, affording cellular and molecular images of living organisms.

On a poignant note, Nobel Laureate Osamu Shimomura was 16 years old and working in a factory just 15 kilometers from Nagasaki, Japan on August 9, 1945.  As a high school student, he watched the U.S. B-29 bomber fly in overhead, and then survived the detonation of the atomic bomb.  Some recent studies based on fluorescent-tagged protein imaging include:

  • Combining optics and genetics to evaluate neural circuit dynamics, with models created of Parkinson’s disease, depression, and behavior relevant to autism
  • Imaging individual mRNA molecules
  • Observation of the dynamics in space and time of nearly 1,000 proteins in individual human cancer cells responding to the chemotherapy drug camptothecin
  • Observing the real-time assembly of individual virions in live cells, from initiation to budding and release
  • Imaging small pancreatic ductal carcinomas and precursor lesions by exploiting cell-surface cancer proteins

The ability to image cells and their microenvironment movedforward with studies such as these:

  • Imaging pH changes in cancer
  • Real-time imaging of cells accompanying cancer
  • Imaging the red-blood-cell membrane changes induced by malaria
  • Developing the MRI pulsing sequences that achieved rapid and accurate internal temperature images

The pursuit of molecular cancer imaging included these advances:

  • Creation of a dual-head dedicated gamma camera used with 99mTc sestamibi to detect breast lesions less than 1 centimeter
  • Development of a high-resolution positron emission mammography/tomography imaging and biopsy device to detect and diagnose breast cancer
  • Engineering of gold nanoparticles targeted to tumor selective antigens, allowing cancer detection at the molecular level using standard CT imaging

As we commence the 2009 edition of The WCC Note, it is our intention to continue keeping you informed of the newest and most seminal imaging-related literature.  Throughout the year, studies will be profiled that may directly or indirectly affect imaging’s role in healthcare.  We will examine new developments in imaging techniques, new hypotheses of disease process, and novel concepts of disease intervention – scientific advances which typically find their way to human use by first being tested in the clinical trial arena.

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Real-Time Imaging, MRI & CT Photography, and MRI: Accurate Temperature – Vol. 2, Number 26

Tuesday, November 11th, 2008

REAL-TIME IMAGING

Dynamic Imaging of Cells Accompanying Cancer Achieved in Mice
Neoplasms contain a microenvironment of multiple other cell types that exist alongside the carcinoma cells.  Termed stromal cells, they include such cells as fibroblasts, lymphocytes, dendritic cells, and macrophages.  These elements combine with extracellular factors, such as growth factor collagen, and oxygen, to form a milieu that evolves along with the carcinoma cells and influences tumor growth.  A recent study sought to image and assess these parallel elements, with the authors developing and using multicolor imaging techniques within a live mouse.  As published in Disease Models & Mechanisms and reported in Science, the authors described designing a spinning disk confocal microscope that achieved image acquisition times of 17 and 33 milliseconds for 512 x 512 and 1024 x 1024 pixel images, respectively.  Led by researchers from the University of California, San Francisco, the study typically collected 32,400 images in a 12-hour period, then documented the location and movement of stromal cells and oxygen’s effect upon them.

Conclusion:  A novel in vivo imaging technique affords high-resolution, four-color, prolonged, real-time imaging of cells that accompany cancer.

MRI & CT PHOTOGRAPHY

Radiologist Wins Lennart Nilsson Award for Scientific PhotographyChimp-3d-photo
The journal Nature recently reported that radiologist Anders Persson of Sweden has won the Lennart Nilsson Award for scientific photography, citing his stunning computer-enhanced 3D images made using new techniques in MRI and CT.  Der. Persson was quoted as saying that technical research should benefit the patient, and that he wanted to show precise and colorful details to achieve that end.  He discussed the utility of imaging in forensic medicine, including the performance of virtual autopsies.  Such post-mortem exams can allow discovery of facts not appreciable in conventional autopsies, such as gas in wounds or small metal particles under the skin.  Persson is currently working on several new facets of medical imaging, including multi-energy CT to visualize the body’s chemical constitution.

Conclusion:  The Lennart Nilsson Award for scientific photography has been awarded to Swedish radiologist Anders Persson.

MRI: ACCURATE TEMPERATURE

MRI Pulsing Sequences Yield Accurate Temperature Imaging
Temperature plays an integral role in medicine.  Its change can reflect metabolism, immune function, and cancer.  For example, digital infared thermal imaging for breast cancer detection was recently reported to show high sensitivity and negative predictive value, depending on the method used.  The current and developing arsenal of various disease therapies includes hyperthermic treatments and thermally sensitive agents that can selectively release drugs based on heat range.  Noting that temperature is a fundamental quality of matter that proves extremely difficult to measure noninvasively below an object’s surface, researchers sought to image it in a broad range of environments with magnetic resonance.  As reported recently in Science, researchers at Princeton and Duke Universities have reported accurate temperature imaging with MRI, using a new pulsing method, and obtained in vivo mouse images.

Conclusion:  Newly developed MRI pulsing sequences can achieve rapid and accurate internal temperature images.

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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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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.

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