Author and Curator: Dror Nir, PhD
As an entrepreneur who is promoting innovations in medical imaging I often find myself confronted with this question. Usually the issue is raised by a project’s potential financier by the way of the following remarks:
- The Genome Project opens the road to “Star Track” kind of medicine. No one will need imaging.
- What about development of new disease-specific markers? Would that put imaging out of business?
- Soon we will have a way to “fix” bad cells’ DNA. and so we will have no use for screening
In these situations I always find myself struggling to come up with answers rather than simply saying, ‘Well, it will take more time for these applications to be available than for you to reach your exit….’. I always try to find a quantitative citation to show how much time and money still needs to be invested before patients will be able to profit from that kind of futuristic “sci-fi medicine”.
Last week, a very recent source for such information was brought to my attention. As a contributor to Leaders in Pharmaceutical Business Intelligence I was asked to review and comment on a recent report published in Nature regarding the progress made in the ENCODE project [1]. I was also asked to assess the influence of the progress in understanding the human genome on imaging-based cancer patients’ management, my field of expertise.
This short report is nicely written and is clear to layman’s (which is what I consider myself in this field) reading. My attention was drawn to some important facts:
- It took 10 years and $288 Million to realise that 80% of 3 Billion DNA bases comprising the human genome serves a purpose.
- So far a very small percentage (3% to 4%) of this potential was uncovered in the scope of this project.
- Already now it is clear that much of the “knowledge” regarding the human genome’s functionality will need to be re-written.
- Researchers anticipate that future studies using advanced technologies will contribute to better estimation of the knowledge gap.
- Good news: these studies are leading to better understanding of diseases’ pathological characteristics and to more accurate reporting of disease sources. This gives hope to future development of disease specific drug development.
So, back to the subject of this post: it seems to me that we are quite a few decades and many billions of dollars away from “Star-Trek medicine”. In the foreseeable future, i.e. at least during my life time (and I hope to live a while longer…), the daily routine of cancer patients’ management will have to rely on workflows constituted of screening, diagnosis, a treatment choice that includes a trial and error type of drugs’ choice, and a long-term post treatment follow-up. Smart imaging promises to increase cost efficiency and medical efficacy of these workflows. And I do hope that our children will benefit from the investment our generation is making in understanding the way the human genome is functioning.
- Science 7 September 2012: Vol. 337 no. 6099 pp. 1159-1161
DOI: 10.1126/science.337.6099.1159 http://www.sciencemag.org/content/337/6099/1159.summary?sid=835cf304-a61f-45d5-8d77-ad44b454e448
Written by Dror Nir
Dr. Nir,
I agree with your conclusions.
In Surgery and Diagnistics done to guide surgical intervention, Medical imaging will prevail.
Fertile ground for Genome related applications will be in genetic testing for identification of new diagnosis of new etiology and potential correction using gene therapy. Genome data is useful for prediction at the patient level propensities fo disease development.
I do not see Medical Imaging to be in any threat from the Genome R&D.
We had a piston PCI potential to decline if prediction for cardiovascular risk can be inferred from Gemone study.
I think that your assessment is quite sobering, and with so much advanced announcements, it is the realistic view. I’ll comment on a few observations.
1. The payment concern about imaging has been the cost and the throughput, as well as too short a replacement cycle because of improvements. It has been especially good for real time response in interventions. The downside has been in the receiver-operator characteristic curve. I would not want to go back to the days when decisions were mostly dependent on clinical judgement with history, physical, traditional x-ray, and manual lab tests [being facetious].
It was a big deal when Art Karmen published on AST and ALT [GOT and GPT] in 1958? You ran it on a spectrophotometer with a coupled reaction at 340 nm.
2. The genomics is exciting, but it would be useless for pharmacology and drug development without tying the findings to dynamic measures of signaling pathways. The story is still not fully transferable to medicine without linking this further to patients. We are at an early stage now.
3. The computational methods used came to life in applied mathematics and computer modeling that is only 10 years old. It’s not just memory on board, but also carrying out nonparametric calculations with a possibility of discovering 50 or more classes, and having 10 predictor variables, and finding the highly information rich predictors. (Beyond the genome)
3. The industrial development of biomarkers has been the driving force in clinical laboratory medicine. But the approach used for the last 30 years was largely based on the “magic bullet”. The definition of MI and the interpretation of troponins has changed by “consensus” several times in the last 5 years.
The way to evidence-based medicine has to be based on primary data.
Dr. Larry,
Thank you for your comment.
It seems that the two of us and Dr. Nir support the current state of Medical Imaging science as having its own reasons for viability and survivability in parallel to the developments on the Gemone fronts.
I believe that the continuing incremental improvements of the Medical Imaging science and technology are sustained by its contributions to Diagnosis prior to Surgical interventions and during surgery.
Will robots replace the surgeons in OR? there are studies on this topic with very favorable results. However, the surgical site is a dynamic theater and only a HUMAN decision maker as Surgeons are will resolve the unexpected discoveries seen as the chest is open.
While we can train a robot to replace an aortic valve to resolve aortic valve (AV) regurgitation, but, if there is a leakage in the blood flow through the heart, starting with blood entering through the vena cave, which was not even discovered prior to the surgery to replace the AV, then ONLY a surgeon with GREAT medical imaging assistance can in parallel deal with BOTH surgeries when the heart is open, no robot will be allowed to complete the valve replacement, since the leakage must be contained in parallel by a second surgeon — this was in an AV replacement case I shadowed at Beth Israel Hospitsl in Boston, in 2008 and a second surgeon from the other OR was called in to work in parallel, one on the leakage and one on the AV replacement.
IMAGING is ALIVE and WELL. Brigham and Women’s Hospital in Boston, CEBI (Center for Evidence-Based Imaging) offers Radiological Informatics Fellowships in three areas.
CEBI-DSG offers funded and non-funded training positions for highly qualified individuals with background in the health sciences, biomedical informatics, computer science, statistics, and mathematics. Faculty from CEBI-DSG teach at Harvard and MIT and also serve as research advisers to graduate and undergraduate students, as well as post-docs.
Goals
Enable individuals with different backgrounds to acquire a level of knowledge and skills in competency areas necessary for pursuing careers in biomedical informatics in academia or industry
Radiologic Imaging
Evidence-based Medicine
Outcomes Research
Probability, Statistics, and Decision Science
Provide a common core curriculum together with a set of experiences shared by all informatics specialization tracks
Facilitate specialized informatics training in particular tracks
Clinical Informatics
Medical Imaging
Public Health Informatics
Bioinformatics
Tracks
There are three main pathways to fellowship training at CEBI-DSG
1. Radiological Informatics Fellowship
Sponsored by a Grant Award to Brigham and Women’s Hospital, Department of Radiology and the Radiological Society of North America (RSNA)
Purpose:
The RSNA Research and Education Foundation Institutional Fellowship in Radiological Informatics was created in response to a present and future need for the training of radiologists in the specific area of information technology as it relates to the radiological sciences. The Fellowship is designed to provide training opportunities to young physicians and scientists in the radiological sciences not yet professionally established in the area of informatics. The specific purposes of the Fellowship are as follows:
To promote and enhance the understanding and utilization of communications capabilities, PACS, internet-based databases and educational materials, and computer linked modalities within radiology departments.
To increase the integration and efficiency of electronic medical applications within radiology departments and hospital environments.
To assist in collaboration with industry in the establishment and implementation of clinical requirements for electronic medical communications.
This one-year fellowship is designed to provide a formally designed training program in radiological informatics consisting of educational, research and experiential components. The goal is to enhance the integration and value of information technologies within medical imaging through increased understanding and utilization of informatics concepts, and to train radiological informaticists for the future of our profession.
It is expected that one or more research projects will be undertaken during the fellowship training period.
Selected fellows will devote full time to the training program under the guidance of a scientific adviser for the full term of the fellowship. Under special circumstances, the fellow may spend a maximum of 20 percent of his/her time in clinical service outside of the proposed training program if the adviser and the fellow agree in advance that those activities are essential to the development of the fellow as an academician.
Fellow Eligibility Requirements:
Have completed their residency or post-doctoral training in the radiological sciences.
Have a degree of M.D., D.O., Ph.D. or equivalent as recognized by the American Medical Association.
2. Boston Biomedical Informatics Research Training (BIRT) Fellowship
Purpose:
The Boston-are Biomedical Informatics Research Training (BIRT) program is a consortium of leading informatics laboratories at Harvard, MIT, Boston University, and Tuffs and is supported by a grant from the National Library of Medicine. BIRT participants comprise a vibrant academic community of individuals with diverse backgrounds and broad-ranging interests, providing fellows with many opportunities for interaction and collaboration. This fellowship provides all trainees with opportunities to learn about the variety of research being conducted at the various laboratories and in the affiliated institutions, as well as in the larger field of biomedical informatics.
Fellow Eligibility Requirements:
US citizen or permanent resident
have a degree of M.D., D.O., Ph.D. or equivalent
3. Evidence-Based Informatics Fellowship
Purpose:
The evidence-based informatics fellowship is integrated with the ACGME – accredited clinical radiological fellowship at the BWH. The fellow is expected to complete at least one year of clinical fellowship in a subspecialty of radiology during the course of their training. In addition, they will complete another year of fellowship at CEBI, with specific focus on evidence-based imaging and imaging informatics. They will also participate in biomedical informatics coursework and seminars.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
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