It has been known for 68 years[1] that early cancer detection can save lives, but currently there is no effective medical imaging device that can detect cancer in all organs of the body with a single examination.
Who’s expert can make a major improvement in the devices for early cancer detection? The oncologist? The biologist? The chemist? The Doctor? Or do we need a breakthrough in medical imaging devices that should be more efficient in detecting cancer at an early stage, in all organs of the body, with a single exam, at a low radiation dose, and at a low examination cost?
Since medical imaging devices rely on detecting particles from radiation, we would need a breakthrough in capturing good signals from radiation so as to lower the dose the patient receives and obtain an effective detection of cancer at the earliest stage before it can take hold.
The focus should be on scientific and technological advancements to implement a low cost screening that is effective for early cancer detection in all organs of the body at a low radiation dose with a single examination at an affordable price. A multimodality device or more than one test efficiently detecting signals confirming the mutation of normal cells into cancerous cells provides valuable information on early cancer detection and in eliminating the likelihood of false positives or false negatives. Among all signals, the most common for most types of cancer is a change in metabolism of cancerous cells that “eats” from 5 to 70 times more nutrients than normal cells. The technique that can measure this difference, invented 60 years ago, called Positron Emission Technology (PET), works by tagging molecules of nutrient (or any other compound such as protein) in body cells with radioisotopes.
This technique[2] provides doctors information on abnormal biological processes (not limited only to abnormal metabolism) even before a morphological change of body tissue takes place. However, the over 5,000 PET/CT devices used in hospitals cannot be used for early cancer detection because of their low efficiency which requires the administration of a high radiation dose to the patient at a high examination cost unaffordable to most people. More importantly, they can only detect already formed medium to large tumors at a stage when the probability for the patient to survive is low.
In 1992, Crosetto invented the 3D-Flow system architecture that is the breakthrough in particle detection that opened the door to other inventions that he made that maximize the discovery of new particles and after the year 2000, to other inventions he made that maximizes the reduction of cancer deaths and cost.
The 3D-Flow basic[3] invention[4] in particle detection is a powerful processing system that has the capability to accurately extract valuable information from data (radiation) arriving from thousands of channels at several million frames per second. Each frame can be processed for a time longer than the interval between two consecutive frames. This invention was formally recognized[5] in 1993 by a major international review[6] at FERMIlab and published in prestigious peer-review scientific journals[7].
The concept of the basic 3D-Flow invention that breaks the speed barrier in real-time applications is described in Figure 1.
Figure 1. Description of one of Crosetto’s innovative concepts that enables acquiring data at a very high input rate while simultaneously allowing necessary time to accurately analyze the information.
This enabled the implementation of a programmable cost-effective object pattern recognition technique that until then could not be envisioned. (See Figure 2).
Figure 2 compares the traditional Trigger Threshold (TT) Technique with the 3D-Flow Object Pattern Recognition Technique (OPRT).
Starting in the year 2000, Crosetto added specific inventions[8] (see Figure 3) in the detector assembly, the photon detection algorithms, coupling the detector with the electronics, providing the possibility to execute complex real-time algorithms exchanging data with neighboring channels with no boundaries in the detector, etc., overcoming the limitation (see Figure 4) of the “Block Detector” by Casey and Nutt that was used in most of the 5,000 PET/CT devices and creating a synergy among all components to build medical imaging devices effective for early cancer detection for asymptomatic people, for cancer survivors and for improving prognosis and therapy (see a summary of the additional inventions for medical imaging applications in Figure 3).
Figure 3. One page summary of the key innovations of the 3D-CBS technology. The key elements are in five main areas. Innovative electronics enables innovations in a different, simplified detector assembly, which in turn enables the innovations in the capability of executing complex real-time algorithms. Additional innovations, such as the ones that enable the use of more economical crystals that allow increased FOV keeping the entire device at a reasonable cost, can be achieved as a result of the combination of the previous innovations
Figure 4. the 3D-CBS detector assembly overcomes the limits in efficiency imposed by the “Block Detector” approach.
This led to the 3D-CBS[9] (3-D Complete Body Screening. See the video[10]) that is a new PET/CT technology, 400 times more efficient than the technology used in the current 5,000 PET (Positron Emission Tomography) devices in capturing more signals at a lower cost per each valid signal captured from tumor markers. It has the potential to replace many tests such as the mammogram, colonoscopy, etc., with an effective single screening test to detect cancer and other diseases in most organs of the body at an early, curable stage. It provides more accurate information about minimum abnormal biological processes, quantified with a ratio between the measured value and the standard value as shown in Figure 6. It is safe to the patient requiring a radiation dose over 10 times less than the 1 mSv approved by the International Commission for Radiation Protection. The increased sensitivity and specificity of the 3D-CBS device makes it possible to have a more accurate staging of the disease, the identification of micro-metastasis, the precise measuring of the cancer activity, inflammation, infections, diabetes, Alzheimer’s, heart and vascular diseases, etc. Its increased sensitivity opens the door to the discovery and development of new biomarkers that cannot be detected with the current inefficient PET (Positron Emission Tomography), thus making their discovery difficult.
Crosetto’s 3D-CBS technology was presented[11] in 2001 in Geneva, Switzerland, at the scientists specialized in the field of physics and medical imaging, it was submitted for public[12] scrutiny and recognized valuable at several international public reviews (e.g. in 2003[13] and in 2008[14]). The superiority[15] in efficiency in saving lives[16] and reducing costs of the 3D-CBS[17] innovative technology was firmly established with scientific calculations and comparisons[18] to other projects, technologies, and approaches during a public, transparent and open scientific procedure[19] at the Leonardo da Vinci competition to identify the most efficient solution in particle detection for early cancer diagnosis. No one could refute the evidence, even when compared to technologies from major research centers such as CERN, FERMIlab and BNL. The rules[20] of the competition, based on the results of an agreed-upon formula for efficiency that eliminated any possible favoritism, were finalized after months of input and comments at the international level.
The concept has been proven[21] by building and testing two modular electronic boards, as shown in Figure 5. The successful testing of the communication between two modular boards proves that a system for HEP of any dimension of the detector and channels can be built, and this applies to PET Medical Imaging applications as well, with all advantages listed above.
Figure 5. Modular board to build a 3D-Flow parallel-Processing system of any dimension for High Energy Physics applications in detecting new particles and in Medical Imaging in reducing cancer deaths and costs.
It is the invention beyond[22] imagination of future science with the highest[23] potential to reduce cancer deaths and cost through an effective early cancer detection compared to any other project (drugs, vaccines, diagnostic devices, education programs to change life style, etc.). Calculations, simulations, logical reasoning and proof of concept of the invention demonstrates to be feasible and functional when it was built and tested in hardware.
Because experimental data[24] show that early detection saves lives in 90% to 98% of the cases, the greater efficiency of the 3D-CBS is estimated to save at least 33% of the lives of those currently dying prematurely of cancer within six years of operation, reaching 50% after ten years and can reduce the cost per each life saved to 1/40. (Results will be measured on a sample population in the age[25] bracket 45-69).
If applied to world population[26], effective early cancer detection has the potential to save 50% of cancer deaths, totaling to over 3 million lives per year, as it has been known and claimed for over 68 years. Implementing the 3D-CBS invention will bend[27] cancer’s exponential cost curve which has currently risen to 100 times[28] the cost of 50 years ago. (In comparison, during the same period, primary food increased only 4 times[29], gasoline increased 10 times[30] and the U.S. National debt[31] 47 times). The increased efficiency of the 3D-CBS can reduce the cancer mortality rate, bending[32] the curve to cross the heart mortality rate.
Preliminary results prove feasibility and functionality of the innovative components of Crosetto’s 3D-CBS invention targeted to effective early cancer detection. His claims and calculations demonstrating the advantages of the very high sensitivity of the 3D-CBS have been also confirmed by third parties after 13 years of denial from the same scientists who prevented Crosetto in the past from presenting his innovative 3D-CBS technology at conferences.
Now these scientists present a similar device, the EXPLORER (which is not suitable to save many lives because is less sensitive and ten times more expensive than the 3D-CBS) at conferences confirming with their calculations and simulations Crosetto’s claims and calculation he published 14 years ago in the book[33] “400+ Times PET Improved Efficiency for Lower-Dose Radiation, Lower-Cost Cancer Screening”. Crosetto distributed his technical-scientific book at no cost to approximately 200 leaders in the field, including authors of the EXPLORER at the 2000 IEEE-NSS-MIC conference in Lyon, France where he also presented two articles[34] on the 3D-CBS technology.
In summary, the ultra-sensitive total body PET screening 3D-CBS device can save many lives because it is a new tool that can provide very accurate information about biological processes that can be tagged with a radioisotope, that:
a) can replace many tests such as the mammogram, colonoscopy, etc., with an effective single low cost, low radiation, screening examination to detect cancer and other diseases in most organs of the body at an early curable stage.
b) provides more accurate information on minimum abnormal biological processes, quantified with a ratio as shown in Fig. 4, not just with colors or gray tones.
c) makes it possible to provide a more accurate staging of the disease and the identification of micro-metastasis.
d) provides a precise measurement of the cancer activity, inflammations, infections, etc.
e) provides the physician with precious information that can explain many anomalies in the patient’s body, not just related to cancer but also to diabetes, Alzheimer’s, heart and vascular diseases, etc.
f) has increased sensitivity, which opens the door to the discovery and development of new biomarkers that cannot now be detected with current inefficient PET, thus making their discovery difficult.
g) physicians will be able to think beyond the size of the tumor as well as how they can use the precious information related to biological processes they receive from the 3D-CBS in their diagnosis and treatment plan.
For all these reasons, the 3D-CBS innovative technology has the potential to save many lives and reduce costs (See the book[35] “The Future is in Our Hands. EVERY YEAR: 10 Million Preventable Deaths and Trillions of Dollars LOST”.
On the left, Figure 6 shows the darker spot that should be interpreted by the physician as an abnormal metabolism, compared to the precise information provided by the 3D-CBS on the right. Besides spotting the body area concerned, the 3D-CBS quantifies abnormal metabolism, showing the ratio between the metabolism measured and the average consumption of nutrient.
Figure 6. Comparison between the information provided by current over 5,000 PET devices and the quantitative information provided by the 3D-CBS device (right on Fig).
References:
[1] National Geographic October 1946. It is known since 68 years that early cancer detection could have saved 50% cancer deaths https://drive.google.com/file/d/0BxWfo2ViJ6r5djY4OU5yd1JoakU/view?usp=sharing
[2] Simple 3-page description of the Positron Emission Technology for laymen: https://drive.google.com/file/d/0BxWfo2ViJ6r5cjFycHRJZ0NGd28/view?usp=sharing
[3] Crosetto’s innovative 3D-Flow architecture for the First Level Trigger summarized in one page https://drive.google.com/file/d/0BxWfo2ViJ6r5UlpTLXhQQjFrZDg/view?usp=sharing
[4] Recognition of the value of Crosetto’s basic invention in this field that he presented in 1992 within 35 days at three international conferences in Europe, Annecy and the U.S. Corpus Christi, TX, Orlando, FL, and published in the prestigious scientific journals: Nuclear Instruments and Methods in Physics Research and IEEE-NSS-MIC. https://drive.google.com/file/d/0BxWfo2ViJ6r5NVBkWVVOcmpMVm8/view?usp=sharing
[5] Recognition of innovations made by Crosetto at a major international scientific review requested by the Director of the Supercollider (also Director of FERMILab), held at Fermilab on December 14, 1993 https://drive.google.com/file/d/0BxWfo2ViJ6r5YUdqVll4ZkVkWTA/view?usp=sharing
[6] Original document reporting in detail how the SSC Deputy Director implements directives from SSC Director, John People, charging Andy Lanford to draft the charges to reviewers of Crosetto’s 3D-Flow innovation. SSC would have to decide at which level Crosetto’s invention should be supported during the SSC close out. Lakford wrote the original document and charged Joel Butler to organize an in depth review. Crosetto’s innovation was considered valuable and received maximum support during the SSC close out to allow Crosetto to: “…complete the current development and leave the project in a state where it could be continued…” Crosetto not only documented his work but he also built, in part at his own expense, the hardware proving feasibility of his innovative concept. However, after 18 years he did not receive funding to build a full system that would benefit HEP and later cancer patients. www.crosettofoundation.org/uploads/419.pdf
[7] Crosetto, D.: 45-page peer-review article published in NIM in 1999. Title: “Base Implementation of the LHCb Trigger Level-0 with the 3D-Flow system,” in Nuclear Instruments and Methods in Physics Research, Sec A, vol. 436 (1999), p.341-385.Part 1: https://drive.google.com/file/d/0BxWfo2ViJ6r5NlVSWHhoTl9jZXc/view?usp=sharing Part 2: https://drive.google.com/file/d/0BxWfo2ViJ6r5ZG82dWRlUVVPWXc/view?usp=sharing
[8] One page summary of the key innovations of the 3D-CBS technology. The key elements are in five main areas. Innovative electronics enables innovations in a different, simplified detector assembly, which in turn enables the innovations in the capability of executing complex real-time algorithms. Additional innovations, such as the ones that enable the use of more economical crystals that allow increased FOV keeping the entire device at a reasonable cost, can be achieved as a result of the combination of the previous innovations. https://drive.google.com/file/d/0BxWfo2ViJ6r5eHIyc0U5SDlTR3c/view?usp=sharing
[9] : Crosetto, D. “Complete Body Screening, 3D-CBS: Features and Implementation”, presented at IEEE-NSS-MIC-2003. Conference Record. M7-129 . https://drive.google.com/file/d/0BxWfo2ViJ6r5RDQ2UURPeHBIYnc/view?usp=sharing
[10] 11-minute video describing the 3D-CBS technology: www.youtube.com/watch?v=HwMnHRuWo4o
[11] Crosetto, D. article presented at the University of Geneva in 2001: https://drive.google.com/file/d/0BxWfo2ViJ6r5Z3RvXzMwZE5URFU/view?usp=sharing
[12] Partial list of the over 6,000 media outlets (newspapers, TV, Radio, on-line new, blogs, etc.) that were sent press releases firstly regarding the request for comments to the rules of the Leonardo da Vinci competition, secondly to submit projects to the competition and thirdly to participate in the scrutiny of the projects under examination. The press releases were sent through BusinessWire, in addition to tens of thousands of emails sent to scientists and people working in the field http://www.leonardodavinciprize.com/elenco_parziale_comunicati_inglese.htm
[13] Final report of the Review of the 3D-CBS innovative technology held in Dallas, TX on July 1, 2003 https://drive.google.com/file/d/0BxWfo2ViJ6r5YURRV1ZMWXc2d2s/view?usp=sharing
[14] Agenda of the international public scientific review of the 3D-CBS innovative technology held on June 23, 2008 in Rome, Italy. www.crosettofoundation.org/uploads/200.pdf.
[15] Minutes of the open meeting held on June 8, 2011 at the University of Pavia, Italy, to determine the winner of the Leonardo da Vinci competition by subjecting each entry to a public scrutiny. https://drive.google.com/file/d/0BxWfo2ViJ6r5VTVlalFlTTFVdjA/view?usp=sharing
[16] Crosetto, D.: article substantiating the benefits in reducing cancer deaths and cost per each life saved: “Ignored Discovery Now Proven Capable of Saving Millions of Lives from Premature Cancer Death Demands Rethinking the Direction of Research” Published in the Book: Astroparticle, Particle and Space Physics, Detectors and Medical Physics Applications. Editor: World Scientific, pp.624-639 – 2008. https://drive.google.com/file/d/0BxWfo2ViJ6r5eDRoUmZ3akJoSEk/view?usp=sharing
[17] Description of the 3D-CBS innovative technology 400 times more efficient than current PET: www.UnitedToEndCancer.org/doc/30.pdf
[18] Comparison in efficiency and cost per photon captured of the 3D-CBS project to CERN Axial-PET, FERMIlab-TOF-PET and BNL-PET projects. https://drive.google.com/file/d/0BxWfo2ViJ6r5YkJzZHhJS1pDbFk/view?usp=sharing.
[19] Leonardo da Vinci Competition for the most efficient solution in particle detection for early cancer diagnosis. http://www.insiemecontroilcancro.org/english.htm.
[20] Rules of the Leonardo da Vinci Competition for the most efficient solution in particle detection for early cancer diagnosis. The winner of the competition is identified based on the results of an agreed upon formula for efficiency that eliminates any possible favoritism: http://www.leonardodavinciprize.com/leonardo_da_vinci_prize.htm, or www.UnitedToEndCancer.org/doc/2.pdf
[21] questionnaire compiled by the inspectors of the ABO Project, who reviewed the entire project for four days in Dallas, TX, during 17 hours of meetings (all videotaped). They approved and witnessed the benefits of the system. See https://drive.google.com/file/d/0BxWfo2ViJ6r5NXdZdXhkenhleVk/view?usp=sharing
[22] 32-page article summarizing Crosetto’s innovations over the last 20 years, which prove to be “beyond the imagination of future science”. The article was presented at the IEEE- NSS- MIC- RTSD conference held in Seoul, Korea, from October 27 to November 2, 2013. Title: “Breaking the Speed Barrier in Real-Time Applications to Make Advances in Particle Detection, Medical and Astrophysics.” IEEE- NSS- MIC- RTSD. Conf Rec R05 -52 , 2013. https://drive.google.com/file/d/0BxWfo2ViJ6r5YXU0MW1QM1IzUW8/view?usp=sharing
[23] One page article submitted at the Conference ” IEEE : the Grand Challenges of Science for Life” – 2-3 December 2013 , Singapore, and at the Workshop “The use of PET in the diagnosis of diseases of the nervous system. News and Perspectives” – January 13, 2014, National Neurological Institute C. Mondino, Pavia. https://drive.google.com/file/d/0BxWfo2ViJ6r5YUFFRHlDdGhFT0U/view?usp=sharing
[24] Experimental results from SEER-NCI-NIH showing that early cancer detection save lives http://www.crosettofoundation.com/uploads/233.pdf
[25] Bar graph comparing world mortality of different causes of death for the year 2008 in the group age 45-69. Source: World Health Organization. Cancer for the 14 years age group 45-69 shows to be highest with 3,555,278 deaths/year (equivalent to a rate of 255 premature deaths every 100,000 people). www.UnitedToEndCancer.org/doc/45.tif.
[26] article. Title: “Logical Reasoning and Reasonable Answers Consistent with Declared Objectives for the Benefit of Mankind.” Presented by Crosetto at the International Seminars on Planetary emergencies 40th Session, Erice, 19-24 August 2008. Editor: World Scientific 2009, p. 531. https://drive.google.com/file/d/0BxWfo2ViJ6r5aWhJTWJJMkFIdFU/view?usp=sharing
[27] The economic cost of cancer treatment in the U.S. The figure shows the exponential increase of cancer cost from 1963 compared to the increase of the price of gasoline and of the U.S. National debt. Source: Brown, ML, Lipscom J., Snyder c., “The Burden of Illness of Cancer: Economic Cost and Quality of Life.” Annual Review of Public Health. 2001, 22:91-113; NHLBI Fact Book, 2001; NCI Fact Book 2003. American Cancer Society, Cancer Facts and Figures; Bureau of the Public Debt, U.S. Treasury; U.S. energy Information Administration Monthly energy Review. Estimated values from 2010 to 2025. See www.UnitedToEndCancer.org/doc/47.tif
[28] Cancer cost in the U.S. during the past 50 years increased by 100 fold. See ACS reports from 1963 to 2010 showing that direct medical expenses for cancer treatment in the U.S. increased 100 times www.crosettofoundation.org/uploads/329.pdf
[29] Primary food in the U.S. during the past 50 years increased only 4 to 5 times (in comparison: bacon went from $0.79/lb to $2.99/lb; eggs from $0.55 dozen to $1.29/dozen, bananas from $0.10/lb to $0.39/lb, hamburger from $0.20 to $0.99, chicken from $0.29/lb to $0.99/lb; onions $0.15/lb to $0.59/lb, etc.)
[30] Gasoline in the U.S. during the past 50 years increased approximately about 10 times (in 1960 the cost was $0.31/gallon, now it is $3.10/gallon).
[31] U.S. National debt increased 47 times during the past 50 years. http://en.wikipedia.org/wiki/United_States_public_debt
[32] Cancer deaths in the U.S. age 50-74 every 100,000 people when compared to heart disease. Source: CDC data until 2007. Estimated values from 2008 to 2025. See www.UnitedToEndCancer.org/doc/48.tif
[33] Crosettto, D.: Technical and Scientific book presented at the IEEE Nuclear Science and Medical Imaging Symposium, Lyon , France, in 2000 , entitled : “Improvement of the Efficiency of the PET 400 Times”, reducing the radiation dose and low-cost screening for cancer. see https://drive.google.com/file/d/0BxWfo2ViJ6r5WVFVWnJteENqMWc/view?usp=sharing
[34] presented to the Conference by Crosetto at IEEE Nuclear Science Symposium and Medical Imaging in Lyon, France, in 2000, the IEEE -2000-563, and IEEE- https://drive.google.com/file/d/0BxWfo2ViJ6r5MTBoTVRucF9CREU/view?usp=sharing 2000-567 https://drive.google.com/file/d/0BxWfo2ViJ6r5d1NENTRkSUg2NVU/view?usp=sharing
[35] 70 page book for laymen entitled: “The Future is in Our Hands . EVERY YEAR : 10 million preventable deaths, trillions of Euros LOST ” https://drive.google.com/file/d/0BxWfo2ViJ6r5RlczdTY3MkFXZDQ/view?usp=sharing