BFR (rocket)

From Wikipedia, the free encyclopedia

BFR

SpaceX rendering of BFR
Function	Mars colonization, Earth–lunar transport, intercontinental transport, orbital launcher[1]
Manufacturer	SpaceX
Country of origin	United States
Cost per launch	US$7 million (external estimate)[2]
Size
Height	106 m (348 ft)[1]
Diameter	9 m (30 ft)
Mass	4,400,000 kg (9,700,000 lb)
Stages	2
Capacity
Payload to LEO	250,000 kg (550,000 lb) expendable[3] 150,000 kg (330,000 lb) reusable[3]
Payload to Earth (return)	50,000 kg (110,000 lb)[1][3]
Launch history
Status	In development
Launch sites	Kennedy LC-39A (potential) South Texas (proposed)
First stage – Booster
Length	58 m (190 ft) [1]
Diameter	9 m (30 ft)
Gross mass	3,065,000 kg (6,757,000 lb)
Engines	31 × Raptor
Thrust	52.7 MN (11,800,000 lbf) sea level [1]
Specific impulse	330 s (3.2 km/s) each engine, sea level
Fuel	Subcooled CH 4 / LOX

Second stage – Spaceship
Length	48 m (157 ft) [1]
Diameter	9 m (30 ft)
Empty mass	85,000 kg (187,000 lb)
Gross mass	1,335,000 kg (2,943,000 lb)
Propellant mass	240,000 kg (530,000 lb) CH 4 860,000 kg (1,900,000 lb) LOX
Engines	7 × Raptor (4 × vacuum, 3 × sea level) [4]
Thrust	12.7 MN (2,900,000 lbf) total
Specific impulse	375 s (3.68 km/s) vacuum each, outer 4 engines 356 s (3.49 km/s) vacuum each, inner 3 engines 330 s (3.2 km/s) sea level [1] each, inner 3 engines
Fuel	Subcooled CH 4 / LOX

BFR^[1]:2:35 is SpaceX's privately funded next-generation launch vehicle and spacecraft announced by Elon Musk in September 2017.^[5][6] It includes reusable launch vehicles and spacecraft that are intended by SpaceX to replace all of the company's existing hardware by the early 2020s, ground infrastructure for rapid launch and relaunch, and zero-gravity propellant transfer technology to be deployed in low Earth orbit (LEO). The new vehicles are much larger than the existing SpaceX fleet. The large payload to Earth orbit of up to 150,000 kg (330,000 lb) makes it a super heavy-lift launch vehicle.

The BFR system is planned to replace the Falcon 9 and Falcon Heavy launch vehicles, as well as the Dragon spacecraft, initially aiming at the Earth-orbit launch market, but explicitly adding substantial capability to support long-duration spaceflight in the cislunar and Mars mission environments.^[1] SpaceX intends this approach to bring significant cost savings that will help the company justify the development expense of designing and building the BFR system.

SpaceX had initially envisioned a larger design known as the ITS launch vehicle, which was presented in September 2016 as part of Musk's vision for an interplanetary transport system.^[7] The ITS range of vehicles was designed with a 12-meter (39 ft) core diameter,^[8] and the BFR design was scaled down to 9 meters (30 ft).^[1] While the ITS had been solely aimed at Mars transit and other interplanetary uses, SpaceX pivoted in 2017 to a plan that would support all SpaceX launch service provider capabilities with a single range of vehicles: Earth-orbit, Lunar-orbit, interplanetary missions, and even intercontinental passenger transport on Earth.^[1][9]

Development work began in 2012 on the Raptor rocket engines which are to be used for both stages of the BFR launch vehicle, and engine testing began in 2016. New rocket engine designs typically have longer lead times than other major parts of new launch vehicles and spacecraft. Tooling for the main tanks has been ordered and a facility to build the vehicles is under construction; construction of the first ship is scheduled to begin in the second quarter of 2018,^[1] with first suborbital flights planned for 2019.^[10] The company publicly stated an aspirational goal for initial Mars-bound cargo flights of BFR launching as early as 2022, followed by the first crewed flight to Mars one synodic period later, in 2024.^[5]

History

As early as 2007, Elon Musk stated a personal goal of eventually enabling human exploration and settlement of Mars,^[11][12] although his personal public interest in Mars goes back at least to 2001.^[13] Bits of additional information about the mission architecture were released in 2011–2015, including a 2014 statement that initial colonists would arrive at Mars no earlier than the middle of the 2020s.^[14] Company statements in 2016 indicated that SpaceX was "being intentionally fuzzy about the timeline ... We're going to try and make as much progress as we can with a very constrained budget."^[15][16]
Musk stated in a 2011 interview that he hoped to send humans to Mars's surface within 10–20 years,^[12] and in late 2012 he stated that he envisioned a Mars colony of tens of thousands with the first colonists arriving no earlier than the middle of the 2020s.^[14][17][18]

Early development

In March 2012, news accounts asserted that a Raptor upper-stage engine had begun development, although details were not released at that time.^[19] In October 2012, Musk publicly stated a high-level plan to build a second reusable rocket system with capabilities substantially beyond the Falcon 9/Falcon Heavy launch vehicles on which SpaceX had by then spent several billion US dollars.^[20] This new vehicle was to be "an evolution of SpaceX's Falcon 9 booster ... 'much bigger'." But Musk indicated that SpaceX would not be speaking publicly about it until 2013.^[14][21]

In June 2013, Musk stated that he intended to hold off any potential initial public offering of SpaceX shares on the stock market until after the "Mars Colonial Transporter is flying regularly."^[22][23]

In August 2014, media sources speculated that the initial flight test of the Raptor-driven super-heavy launch vehicle could occur as early as 2020, in order to fully test the engines under orbital spaceflight conditions; however, any colonization effort was reported to continue to be "deep into the future".^[24][25]

In early 2015, Musk said that he hoped to release details in late 2015 of the "completely new architecture" for the system that would enable the colonization of Mars. Those plans were delayed,^{[26][27][28][16][29]} and the name of the system architecture was changed to "Interplanetary Transport System" (ITS) in mid-September 2016.^[7]

On 27 September 2016, at the 67th annual meeting of the International Astronautical Congress, Musk unveiled substantial details of the design for the transport vehicles. The details included the very large size (12 meters (39 ft) core diameter),^[8] construction material, number and type of engines, thrust, cargo and passenger payload capabilities, in-orbit propellant-tanker refills, representative transit times, and portions of the Mars-side and Earth-side infrastructure that SpaceX intends to build to support a set of three flight vehicles. The three distinct vehicles that made up the ITS launch vehicle in the 2016 design were the:^[1]

• ITS booster, the first-stage of the launch vehicle
• ITS spaceship, a second-stage and long-duration in-space spacecraft
• ITS tanker, an alternative second-stage designed to carry more propellant for refueling other vehicles in space

In addition, Musk championed a larger systemic vision, a vision for a bottom-up emergent order of other interested parties—whether companies, individuals, or governments—to utilize the new and radically lower-cost transport infrastructure that SpaceX would endeavor to build in order to help build a sustainable human civilization on Mars by innovating and meeting the demand that such a growing venture would occasion.^[30][31]

In the November 2016 plan, SpaceX indicated it would fly its earliest research spacecraft missions to Mars using its Falcon Heavy launch vehicle and a specialized modified Dragon spacecraft, called "Red Dragon" prior to the completion, and first launch, of any ITS launch vehicle. Later Mars missions using ITS were slated at that time to begin no earlier than 2022.^[32]

By February 2017, the earliest launch of any SpaceX mission to Mars was to be 2020, two years later than the previously mentioned 2018 Falcon Heavy/Dragon2 exploratory mission.^[33] In July 2017, SpaceX announced it no longer plans to use a propulsively-landed Red Dragon spacecraft on the early missions, as had been previously announced.^[34]

In July 2017, SpaceX made public its plan to build a much smaller launch vehicle and spacecraft before building the ITS launch vehicle that had been unveiled nine months earlier designed explicitly for the beyond-Earth-orbit (BEO) part of future SpaceX launch service offerings. Musk indicated that the architecture had "evolved quite a bit" since the November 2016 articulation of the comprehensive Mars architecture. A key driver of the new architecture was to be making the new system useful for substantial Earth-orbit and cislunar launches so that the new system might pay for itself, in part, through economic spaceflight activities in the near-Earth space zone.^[35] ITS development was put on hold and "Serious development of BFR" began in 2017.^[1]:15:22

Announcement of the BFR

BFR compared to other systems

On 29 September 2017 at the 68th annual meeting of the International Astronautical Congress in Adelaide, South Australia, SpaceX unveiled the new smaller vehicle architecture. Musk said "we are searching for the right name, but the code name, at least, is BFR."^[1] The new launch vehicle system is a 9-meter (30 ft) diameter technology, using methalox-fueled Raptor rocket engine technology directed initially at the Earth-orbit and cislunar environment, later, being used for Mars missions.^[1][5]

Aerodynamics of the BFR second stage changed from the 2016-design ITS launch vehicle. The new design is cylindrical with a small delta wing at the rear end which includes a split flap for pitch and roll control. The delta wing and split flaps are needed to expand the mission envelope to allow the ship to land in a variety of atmospheric densities (no, thin, or heavy atmosphere) with a wide range of payloads (small, heavy, or none) in the nose of the ship.^{[1]:18:05–19:25} The cylindrical shape is for mass optimization.

There are three versions of the ship: BFR crew, BFR tanker, BFR cargo. The cargo version can also be used to launch satellites to low Earth orbit.

After retanking in a high-elliptic Earth orbit the spaceship is being designed to be able to land on the Moon and return to Earth without further refueling.^[1]:31:50 The most surprising announcement was to use BFR as a point-to-point transfer system for people on Earth. Musk expects ticket price to be on par with a full-fare economy plane ticket for the same distance.

As of September 2017, Raptor engines had been tested for a combined total of 1200 seconds of test firing time over 42 main engine tests. The longest test was 100 seconds, which is limited by the size of the propellant tanks at the SpaceX ground test facility. The test engine operates at 20 MPa (200 bar; 2,900 psi) pressure. The flight engine is aimed for 25 MPa (250 bar; 3,600 psi), and SpaceX expects to achieve 30 MPa (300 bar; 4,400 psi) in later iterations.^[1]

Testing of the BFR vehicle is expected to begin with short suborbital hops of the full-scale ship, likely to be just a few hundred kilometers altitude and lateral distance.^[36]

By September 2017, SpaceX had already started building launch vehicle components. "The tooling for the main tanks has been ordered, the facility is being built, we will start construction of the first ship [in the second quarter of 2018.]" Musk is hoping to be ready for an initial Mars launch in five years, in order to make the 2022 Mars conjunction window.^[1] In November 2017, SpaceX president and COO Gwynne Shotwell indicated that approximately half of all current development work on BFR is on Raptor engine development.^[37]

The aspirational goal is the first two cargo missions to Mars in 2022, with the goal to "confirm water resources and identify hazards" while putting "power, mining, and life support infrastructure" in place for future flights, followed by four ships in 2024, two crewed BFR spaceships plus two cargo-only ships bringing additional equipment and supplies with the goal of setting up the propellant production plant.^[1]

Nomenclature

The descriptor for the large SpaceX Mars rocket has varied over the past five years that SpaceX has publicly-released information about the project. "BFR" is the current code name for SpaceX's privately funded launch vehicle announced by Elon Musk in September 2017.^{[1]:2:39[5][6][38][39][40]} SpaceX President Gwynne Shotwell has stated the BFR code stands for "Big Falcon Rocket".^[41] However, Elon Musk has explained that although this is the official name, he drew inspiration from the BFG weapon in the Doom video games.^[42]

From September 2016 through August 2017, the overall system was referred to by SpaceX as the Interplanetary Transport System and the launch vehicle itself as the ITS launch vehicle. Beginning in mid-2013, and prior to September 2016, SpaceX had referred to both the architecture and the vehicle as the Mars Colonial Transporter.

Scope of BFR missions

The BFR launch vehicle is planned to replace all existing SpaceX vehicles and spacecraft in the early 2020s. SpaceX cost estimation has led the company to conclude that BFR launches will be cheaper per launch than launches of the existing vehicles and even cheaper than launches of the retired Falcon 1. This is partly due to the full reusability of all parts of BFR, and partly due to precision landing of the booster on its launch mount and industry-leading launch operations. More specifically, both Falcon 9 and Falcon Heavy launch vehicles and the Dragon spacecraft flown in February 2018 will be replaced in the operational SpaceX fleet during the early 2020s.^{[43][1]:24:50–27:05}

Flight missions of BFR will thus aim at the:^[43]

• legacy Earth-orbit market
• long-duration spaceflight missions in the cislunar region
• Mars missions, both as cargo ships as well as passenger-carrying transport
• long-distance commercial travel on Earth: the ability to transport people on point-to-point suborbital flights between two points on Earth in under one hour.^[36][44] Musk refers to this as "Earth-to-Earth".^[45]

Description

The BFR design combines several elements that, according to Musk, will make long-duration, beyond Earth orbit (BEO) spaceflights possible. They will reduce the per-ton cost of launches to low Earth orbit (LEO) and of transportation between BEO destinations. They will also serve all usage for the conventional LEO market. This will allow SpaceX to focus the majority of their development resources on the next-generation launch vehicle.^[1][9][46]

The fully-reusable super-heavy-lift BFR will consist of a:^[1]

• "BFR booster": a reusable booster stage.
• a reusable, integrated second-stage-with-spaceship, which will be built in at least three versions:
  • "BFR spaceship": a large, long-duration spaceship capable of carrying passengers or cargo to interplanetary destinations, to LEO, or between destinations on Earth.
  • "BFR tanker": an Earth-orbit, cargo-only propellant tanker to support the refilling of propellants in orbit. The tanker will enable a long-duration spaceship to serve as the second stage of the launch vehicle while expending almost all of its propellant to reach LEO. After refilling in orbit, the spaceship will provide a significant amount of the energy needed to put it onto an interplanetary trajectory.
  • "BFR satellite delivery spacecraft": will have a large cargo bay door that can open in space to facilitate the placement of large and small spacecraft into orbit.

Combining the second-stage of a launch vehicle with a long-duration spaceship will be a unique type of space mission architecture. This architecture is dependent on the successful refilling of propellants in orbit.

The BFR spaceship, the BFR tanker, and the BFR satellite delivery spacecraft will have the same outer mold line. The second-stage-spaceship will be capable of returning to the launch location. While returning, it will be able to tolerate multiple engine-out events and land successfully with just one operating engine.^[1]

The functioning of the system during BEO launches to Mars will include propellant production on the Mars surface. This is necessary for the return trip and to reuse the spaceship at a minimal cost. Lunar destinations will be possible without Lunar-propellant depots, so long as the spaceship is refueled in a high-elliptical orbit before the Lunar transit begins.^[1]

The major characteristics of the launch vehicle will include the following.^[1][47][3]

• Both stages will be completely reusable.
• The booster will return to land on the launch mount. The second-stage/spaceship will have the ability to return to near the launch mount. Both will use retropropulsive landing and the reusable LV technologies developed earlier by SpaceX.
• The expected landing reliability will be on a par with major airliners.
• Rendezvous and docking will be automated.
• There will be on-orbit propellant transfers from BFR tankers to BFR spaceships.
• A spaceship and its payload will be able to transit to the Moon or fly to Mars after an on-orbit propellant loading.
• Heat-shields will be reusable.
• The BFR spaceship will have a pressurized volume of 825 m³ (29,100 cu ft), with up to 40 cabins, large common areas, central storage, a galley, and a solar storm shelter for Mars missions.

Specifications^[1][47]

Component Attribute	Complete	BFR booster	BFR spaceship/tanker/ sat-delivery vehicle
LEO Payload	150,000 kg (330,000 lb)[3]
Return Payload			50,000 kg (110,000 lb)[3]
Cargo Volume	825 m3 (29,100 cu ft)[3]	N/A	825 m3 (29,100 cu ft)[3] (spaceship)
Diameter	9 m (30 ft)[3]
Length	106 m (348 ft)	58 m (190 ft)	48 m (157 ft)[3]
Maximum weight	4,400,000 kg (9,700,000 lb)[3]		1,335,000 kg (2,943,000 lb)
Propellant Capacity			CH 4 – 240,000 kg (530,000 lb)
			O 2 – 860,000 kg (1,900,000 lb)
Empty weight			85,000 kg (187,000 lb)[3]
Engines		31 × SL Raptors	3 × SL + 4 × vacuum Raptors[4]
Thrust		52.7 MN (11,800,000 lbf)	12.7 MN (2,900,000 lbf) total

The Raptor engine will operate at 25 MPa (250 bar; 3,600 psi) of chamber pressure and achieve 30 MPa (300 bar; 4,400 psi) in later iterations. The engine will be designed with an extreme focus on reliability.^[1][47]

Manufacturing the BFR

Construction of the initial BFR vehicle will be in a new factory to be built on the Los Angeles waterfront^[48] in the San Pedro area.^[49]

Positron emission tomography

From Wikipedia, the free encyclopedia

 

Positron Emission Tomography
Image of a typical positron emission tomography (PET) facility
ICD-10-PCS	C?3
ICD-9-CM	92.0-92.1
MeSH	D049268
OPS-301 code	3-74
MedlinePlus	003827

Positron-emission tomography (PET)^[1] is a nuclear medicine functional imaging technique that is used to observe metabolic processes in the body as an aid to the diagnosis of disease. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. Three-dimensional images of tracer concentration within the body are then constructed by computer analysis. In modern PET-CT scanners, three-dimensional imaging is often accomplished with the aid of a CT X-ray scan performed on the patient during the same session, in the same machine.

If the biologically active molecule chosen for PET is fludeoxyglucose (FDG), an analogue of glucose, the concentrations of tracer imaged will indicate tissue metabolic activity as it corresponds to the regional glucose uptake. Use of this tracer to explore the possibility of cancer metastasis (i.e., spreading to other sites) is the most common type of PET scan in standard medical care (90% of current scans). Less often, other radioactive tracers are used to image the tissue concentration of other types of molecules of interest. One of the disadvantages of PET scanners is their operating cost.^[2]

Uses

PET/CT-System with 16-slice CT; the ceiling mounted device is an injection pump for CT contrast agent

Whole-body PET scan using ¹⁸F-FDG

PET is both a medical and research tool. It is used heavily in clinical oncology (medical imaging of tumours and the search for metastases), and for clinical diagnosis of certain diffuse brain diseases such as those causing various types of dementias. PET is also an important research tool to map normal human brain and heart function, and support drug development.

PET is also used in pre-clinical studies using animals, where it allows repeated investigations into the same subjects. This is particularly valuable in cancer research, as it results in an increase in the statistical quality of the data (subjects can act as their own control) and substantially reduces the numbers of animals required for a given study.

Alternative methods of scanning include x-ray computed tomography (CT), magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI), ultrasound and single-photon emission computed tomography (SPECT).

While some imaging scans such as CT and MRI isolate organic anatomic changes in the body, PET and SPECT are capable of detecting areas of molecular biology detail (even prior to anatomic change). PET scanning does this using radiolabelled molecular probes that have different rates of uptake depending on the type and function of tissue involved. Changing of regional blood flow in various anatomic structures (as a measure of the injected positron emitter) can be visualized and relatively quantified with a PET scan.

PET imaging is best performed using a dedicated PET scanner. It is also possible to acquire PET images using a conventional dual-head gamma camera fitted with a coincidence detector. Although the quality of gamma-camera PET is considerably lower and acquisition is slower, this method allows institutions with low demand for PET to provide on-site imaging, instead of referring patients to another centre or relying on a visit by a mobile scanner.

Oncology

PET scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG), called FDG-PET, is widely used in clinical oncology. This tracer is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form is greatly elevated in rapidly growing malignant tumors). A typical dose of FDG used in an oncological scan has an effective radiation dose of 14 mSv.^[3] Because the oxygen atom that is replaced by F-18 to generate FDG is required for the next step in glucose metabolism in all cells, no further reactions occur in FDG. Furthermore, most tissues (with the notable exception of liver and kidneys) cannot remove the phosphate added by hexokinase. This means that FDG is trapped in any cell that takes it up until it decays, since phosphorylated sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the brain, the liver, and most cancers. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin's lymphoma, non-Hodgkin lymphoma, and lung cancer.^{[citation needed]}

A few other isotopes and radiotracers are slowly being introduced into oncology for specific purposes. For example, ¹¹C-labelled metomidate (11C-metomidate), has been used to detect tumors of adrenocortical origin.^[4][5] Also, FDOPA PET-CT, in centers which offer it, has proven to be a more sensitive alternative to finding, and also localizing, pheochromocytoma than the MIBG scan.^[6][7][8]

Neuroimaging

• 
  PET scan of the human brain

• Neurology: PET neuroimaging is based on an assumption that areas of high radioactivity are associated with brain activity. What is actually measured indirectly is the flow of blood to different parts of the brain, which is, in general, believed to be correlated, and has been measured using the tracer oxygen-15. Because of its 2-minute half-life, O-15 must be piped directly from a medical cyclotron for such uses, which is difficult. In practice, since the brain is normally a rapid user of glucose, and since brain pathologies such as Alzheimer's disease greatly decrease brain metabolism of both glucose and oxygen in tandem, standard FDG-PET of the brain, which measures regional glucose use, may also be successfully used to differentiate Alzheimer's disease from other dementing processes, and also to make early diagnoses of Alzheimer's disease. The advantage of FDG-PET for these uses is its much wider availability. PET imaging with FDG can also be used for localization of seizure focus: A seizure focus will appear as hypometabolic during an interictal scan. Several radiotracers (i.e. radioligands) have been developed for PET that are ligands for specific neuroreceptor subtypes such as [¹¹C] raclopride, [¹⁸F] fallypride and [¹⁸F] desmethoxyfallypride for dopamine D2/D3 receptors, [¹¹C] McN 5652 and [¹¹C] DASB for serotonin transporters, [¹⁸F] Mefway for serotonin 5HT1A receptors, [¹⁸F] Nifene for nicotinic acetylcholine receptors or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses.

The development of a number of novel probes for noninvasive, in vivo PET imaging of neuroaggregate in human brain has brought amyloid imaging to the doorstep of clinical use. The earliest amyloid imaging probes included 2-(1-{6-[(2-[¹⁸F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([¹⁸F]FDDNP)^[9] developed at the University of California, Los Angeles and N-methyl-[¹¹C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole^[10] (termed Pittsburgh compound B) developed at the University of Pittsburgh. These amyloid imaging probes permit the visualization of amyloid plaques in the brains of Alzheimer's patients and could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies. [¹¹C]PMP (N-[¹¹C]methylpiperidin-4-yl propionate) is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetylcholinergic neurotransmitter system by acting as a substrate for acetylcholinesterase. Post-mortem examination of AD patients have shown decreased levels of acetylcholinesterase. [¹¹C]PMP is used to map the acetylcholinesterase activity in the brain, which could allow for pre-mortem diagnoses of AD and help to monitor AD treatments.^[11] Avid Radiopharmaceuticals of Philadelphia has developed a compound called 18F-AV-45 that uses the longer-lasting radionuclide fluorine-18 to detect amyloid plaques using PET scans.^[12]

• Neuropsychology / Cognitive neuroscience: To examine links between specific psychological processes or disorders and brain activity.
  
• Psychiatry: Numerous compounds that bind selectively to neuroreceptors of interest in biological psychiatry have been radiolabeled with C-11 or F-18. Radioligands that bind to dopamine receptors (D1,^[13] D2 receptor,^[14][15] reuptake transporter), serotonin receptors (5HT1A, 5HT2A, reuptake transporter) opioid receptors (mu) and other sites have been used successfully in studies with human subjects. Studies have been performed examining the state of these receptors in patients compared to healthy controls in schizophrenia, substance abuse, mood disorders and other psychiatric conditions.
  
• Stereotactic surgery and radiosurgery: PET-image guided surgery facilitates treatment of intracranial tumors, arteriovenous malformations and other surgically treatable conditions.^[16]

Cardiology

Cardiology, atherosclerosis and vascular disease study: In clinical cardiology, FDG-PET can identify so-called "hibernating myocardium", but its cost-effectiveness in this role versus SPECT is unclear. FDG-PET imaging of atherosclerosis to detect patients at risk of stroke is also feasible and can help test the efficacy of novel anti-atherosclerosis therapies.^[17]

Infectious diseases

Imaging infections with molecular imaging technologies can improve diagnosis and treatment follow-up. PET has been widely used to image bacterial infections clinically by using fluorodeoxyglucose (FDG) to identify the infection-associated inflammatory response.

Three different PET contrast agents have been developed to image bacterial infections in vivo: [¹⁸F]maltose,^[18] [¹⁸F]maltohexaose and [¹⁸F]2-fluorodeoxysorbitol (FDS).^[19] FDS has also the added benefit of being able to target only Enterobacteriaceae.

Pharmacokinetics

Pharmacokinetics: In pre-clinical trials, it is possible to radiolabel a new drug and inject it into animals. Such scans are referred to as biodistribution studies. The uptake of the drug, the tissues in which it concentrates, and its eventual elimination, can be monitored far more quickly and cost effectively than the older technique of killing and dissecting the animals to discover the same information. Much more commonly, drug occupancy at a purported site of action can be inferred indirectly by competition studies between unlabeled drug and radiolabeled compounds known apriori to bind with specificity to the site. A single radioligand can be used this way to test many potential drug candidates for the same target. A related technique involves scanning with radioligands that compete with an endogenous (naturally occurring) substance at a given receptor to demonstrate that a drug causes the release of the natural substance.^{[citation needed]}

Small animal imaging

PET technology for small animal imaging: A miniature PE tomograph has been constructed that is small enough for a fully conscious and mobile rat to wear on its head while walking around.^[20] This RatCAP (Rat Conscious Animal PET) allows animals to be scanned without the confounding effects of anesthesia. PET scanners designed specifically for imaging rodents, often referred to as microPET, as well as scanners for small primates, are marketed for academic and pharmaceutical research. The scanners are apparently based on microminiature scintillators and amplified avalanche photodiodes (APDs) through a new system recently invented uses single chip silicon photomultipliers.

Musculo-skeletal imaging

Musculoskeletal imaging: PET has been shown to be a feasible technique for studying skeletal muscles during exercises like walking.^[21] One of the main advantages of using PET is that it can also provide muscle activation data about deeper lying muscles such as the vastus intermedialis and the gluteus minimus, as compared to other muscle studying techniques like electromyography, which can be used only on superficial muscles (i.e., directly under the skin). A clear disadvantage is that PET provides no timing information about muscle activation because it has to be measured after the exercise is completed. This is due to the time it takes for FDG to accumulate in the activated muscles.

Safety

PET scanning is non-invasive, but it does involve exposure to ionizing radiation.^[2]
18F-FDG, which is now the standard radiotracer used for PET neuroimaging and cancer patient management,^[22] has an effective radiation dose of 14 mSv.^[3]

The amount of radiation in 18F-FDG is similar to the effective dose of spending one year in the American city of Denver, Colorado (12.4 mSv/year).^[23] For comparison, radiation dosage for other medical procedures range from 0.02 mSv for a chest x-ray and 6.5–8 mSv for a CT scan of the chest.^[24][25] Average civil aircrews are exposed to 3 mSv/year,^[26] and the whole body occupational dose limit for nuclear energy workers in the USA is 50mSv/year.^[27] For scale, see Orders of magnitude (radiation).

For PET-CT scanning, the radiation exposure may be substantial—around 23–26 mSv (for a 70 kg person—dose is likely to be higher for higher body weights).^[28]

Operation

Schematic view of a detector block and ring of a PET scanner

Radionuclides and radiotracers

Radionuclides used in PET scanning are typically isotopes with short half-lives ^[2] such as carbon-11 (~20 min), nitrogen-13 (~10 min), oxygen-15 (~2 min), fluorine-18 (~110 min), gallium-68 (~67 min), zirconium-89 (~78.41 hours), or rubidium-82(~1.27 min). These radionuclides are incorporated either into compounds normally used by the body such as glucose (or glucose analogues), water, or ammonia, or into molecules that bind to receptors or other sites of drug action. Such labelled compounds are known as radiotracers. PET technology can be used to trace the biologic pathway of any compound in living humans (and many other species as well), provided it can be radiolabeled with a PET isotope. Thus, the specific processes that can be probed with PET are virtually limitless, and radiotracers for new target molecules and processes are continuing to be synthesized; as of this writing there are already dozens in clinical use and hundreds applied in research. At present,^[when?] by far the most commonly used radiotracer in clinical PET scanning is fluorodeoxyglucose (also called FDG or fludeoxyglucose), an analogue of glucose that is labeled with fluorine-18. This radiotracer is used in essentially all scans for oncology and most scans in neurology, and thus makes up the large majority of all of the radiotracer (> 95%) used in PET and PET-CT scanning.
Due to the short half-lives of most positron-emitting radioisotopes, the radiotracers have traditionally been produced using a cyclotron in close proximity to the PET imaging facility. The half-life of fluorine-18 is long enough that radiotracers labeled with fluorine-18 can be manufactured commercially at offsite locations and shipped to imaging centers. Recently rubidium-82 generators have become commercially available.^[29] These contain strontium-82, which decays by electron capture to produce positron-emitting rubidium-82.

Emission

To conduct the scan, a short-lived radioactive tracer isotope is injected into the living subject (usually into blood circulation). Each tracer atom has been chemically incorporated into a biologically active molecule. There is a waiting period while the active molecule becomes concentrated in tissues of interest; then the subject is placed in the imaging scanner. The molecule most commonly used for this purpose is F-18 labeled fluorodeoxyglucose (FDG), a sugar, for which the waiting period is typically an hour. During the scan, a record of tissue concentration is made as the tracer decays.

Schema of a PET acquisition process

As the radioisotope undergoes positron emission decay (also known as positive beta decay), it emits a positron, an antiparticle of the electron with opposite charge. The emitted positron travels in tissue for a short distance (typically less than 1 mm, but dependent on the isotope^[30]), during which time it loses kinetic energy, until it decelerates to a point where it can interact with an electron.^[31] The encounter annihilates both electron and positron, producing a pair of annihilation (gamma) photons moving in approximately opposite directions. These are detected when they reach a scintillator in the scanning device, creating a burst of light which is detected by photomultiplier tubes or silicon avalanche photodiodes (Si APD). The technique depends on simultaneous or coincident detection of the pair of photons moving in approximately opposite directions (they would be exactly opposite in their center of mass frame, but the scanner has no way to know this, and so has a built-in slight direction-error tolerance). Photons that do not arrive in temporal "pairs" (i.e. within a timing-window of a few nanoseconds) are ignored.

Localization of the positron annihilation event

The most significant fraction of electron–positron annihilations results in two 511 keV gamma photons being emitted at almost 180 degrees to each other; hence, it is possible to localize their source along a straight line of coincidence (also called the line of response, or LOR). In practice, the LOR has a non-zero width as the emitted photons are not exactly 180 degrees apart. If the resolving time of the detectors is less than 500 picoseconds rather than about 10 nanoseconds, it is possible to localize the event to a segment of a chord, whose length is determined by the detector timing resolution. As the timing resolution improves, the signal-to-noise ratio (SNR) of the image will improve, requiring fewer events to achieve the same image quality. This technology is not yet common, but it is available on some new systems.^[32]

Image reconstruction

The raw data collected by a PET scanner are a list of 'coincidence events' representing near-simultaneous detection (typically, within a window of 6 to 12 nanoseconds of each other) of annihilation photons by a pair of detectors. Each coincidence event represents a line in space connecting the two detectors along which the positron emission occurred (i.e., the line of response (LOR)).

Analytical techniques, much like the reconstruction of computed tomography (CT) and single-photon emission computed tomography (SPECT) data, are commonly used, although the data set collected in PET is much poorer than CT, so reconstruction techniques are more difficult. Coincidence events can be grouped into projection images, called sinograms. The sinograms are sorted by the angle of each view and tilt (for 3D images). The sinogram images are analogous to the projections captured by computed tomography (CT) scanners, and can be reconstructed in a similar way. The statistics of data thereby obtained are much worse than those obtained through transmission tomography. A normal PET data set has millions of counts for the whole acquisition, while the CT can reach a few billion counts. This contributes to PET images appearing "noisier" than CT. Two major sources of noise in PET are scatter (a detected pair of photons, at least one of which was deflected from its original path by interaction with matter in the field of view, leading to the pair being assigned to an incorrect LOR) and random events (photons originating from two different annihilation events but incorrectly recorded as a coincidence pair because their arrival at their respective detectors occurred within a coincidence timing window).

In practice, considerable pre-processing of the data is required—correction for random coincidences, estimation and subtraction of scattered photons, detector dead-time correction (after the detection of a photon, the detector must "cool down" again) and detector-sensitivity correction (for both inherent detector sensitivity and changes in sensitivity due to angle of incidence).

Filtered back projection (FBP) has been frequently used to reconstruct images from the projections. This algorithm has the advantage of being simple while having a low requirement for computing resources. Disadvantages are that shot noise in the raw data is prominent in the reconstructed images, and areas of high tracer uptake tend to form streaks across the image. Also, FBP treats the data deterministically—it does not account for the inherent randomness associated with PET data, thus requiring all the pre-reconstruction corrections described above.

Statistical, likelihood-based approaches: Statistical, likelihood-based ^{[33] [34]} iterative expectation-maximization algorithms such as the Shepp-Vardi algorithm^[35] are now the preferred method of reconstruction. These algorithms compute an estimate of the likely distribution of annihilation events that led to the measured data, based on statistical principles. The advantage is a better noise profile and resistance to the streak artifacts common with FBP, but the disadvantage is higher computer resource requirements. A further advantage of statistical image reconstruction techniques is that the physical effects that would need to be pre-corrected for when using an analytical reconstruction algorithm, such as scattered photons, random coincidences, attenuation and detector dead-time, can be incorporated into the likelihood model being used in the reconstruction, allowing for additional noise reduction. Iterative reconstruction has also been shown to result in improvements in the resolution of the reconstructed images, since more sophisticated models of the scanner Physics can be incorporated into the likelihood model than those used by analytical reconstruction methods, allowing for improved quantification of the radioactivity distribution.^[36]

Research has shown that Bayesian methods that involve a Poisson likelihood function and an appropriate prior probability (e.g., a smoothing prior leading to total variation regularization or a Laplacian distribution leading to ${\displaystyle \ell _{1}}$-based regularization in a wavelet or other domain), such as via Ulf Grenander's Sieve estimator^{[37] [38]} or via Bayes penalty methods ^{[39] [40]} or via I.J. Good's roughness method ^[41] ,^[42] may yield superior performance to expectation-maximization-based methods which involve a Poisson likelihood function but do not involve such a prior.^[43][44][45]

Attenuation correction: Quantitative PET Imaging requires attenuation correction^[46]. In these systems attenuation correction is based on a transmission scan using ⁶⁸Ge rotating rod source^[47].
transmission scans directly measure attenuation values at 511keV^[48]. Attenuation occurs when photons emitted by the radiotracer inside the body are absorbed by intervening tissue between the detector and the emission of the photon. As different LORs must traverse different thicknesses of tissue, the photons are attenuated differentially. The result is that structures deep in the body are reconstructed as having falsely low tracer uptake. Contemporary scanners can estimate attenuation using integrated x-ray CT equipment, in place of earlier equipment that offered a crude form of CT using a gamma ray (positron emitting) source and the PET detectors.

While attenuation-corrected images are generally more faithful representations, the correction process is itself susceptible to significant artifacts. As a result, both corrected and uncorrected images are always reconstructed and read together.

2D/3D reconstruction: Early PET scanners had only a single ring of detectors, hence the acquisition of data and subsequent reconstruction was restricted to a single transverse plane. More modern scanners now include multiple rings, essentially forming a cylinder of detectors.

There are two approaches to reconstructing data from such a scanner: 1) treat each ring as a separate entity, so that only coincidences within a ring are detected, the image from each ring can then be reconstructed individually (2D reconstruction), or 2) allow coincidences to be detected between rings as well as within rings, then reconstruct the entire volume together (3D).

3D techniques have better sensitivity (because more coincidences are detected and used) and therefore less noise, but are more sensitive to the effects of scatter and random coincidences, as well as requiring correspondingly greater computer resources. The advent of sub-nanosecond timing resolution detectors affords better random coincidence rejection, thus favoring 3D image reconstruction.

Time-of-flight (TOF) PET: For modern systems with a higher time resolution (roughly 3 nanoseconds) a technique called "Time-of-flight" is used to improve the overall performance. Time-of-flight PET makes use of very fast gamma-ray detectors and data processing system which can more precisely decide the difference in time between the detection of the two photons. Although it is technically impossible to localize the point of origin of the annihilation event exactly (currently within 10 cm) thus image reconstruction is still needed, TOF technique gives a remarkable improvement in image quality, especially signal-to-noise ratio.

Complete body PET-CT fusion image

Brain PET-MRI fusion image

Combination of PET with CT or MRI

PET scans are increasingly read alongside CT or magnetic resonance imaging (MRI) scans, with the combination (called "co-registration") giving both anatomic and metabolic information (i.e., what the structure is, and what it is doing biochemically). Because PET imaging is most useful in combination with anatomical imaging, such as CT, modern PET scanners are now available with integrated high-end multi-detector-row CT scanners (so-called "PET-CT"). Because the two scans can be performed in immediate sequence during the same session, with the patient not changing position between the two types of scans, the two sets of images are more precisely registered, so that areas of abnormality on the PET imaging can be more perfectly correlated with anatomy on the CT images. This is very useful in showing detailed views of moving organs or structures with higher anatomical variation, which is more common outside the brain.
At the Jülich Institute of Neurosciences and Biophysics, the world's largest PET-MRI device began operation in April 2009: a 9.4-tesla magnetic resonance tomograph (MRT) combined with a positron emission tomograph (PET). Presently, only the head and brain can be imaged at these high magnetic field strengths.^[49]

For brain imaging, registration of CT, MRI and PET scans may be accomplished without the need for an integrated PET-CT or PET-MRI scanner by using a device known as the N-localizer.^{[16][50][51][52]}

Limitations

The minimization of radiation dose to the subject is an attractive feature of the use of short-lived radionuclides. Besides its established role as a diagnostic technique, PET has an expanding role as a method to assess the response to therapy, in particular, cancer therapy,^[53] where the risk to the patient from lack of knowledge about disease progress is much greater than the risk from the test radiation.

Limitations to the widespread use of PET arise from the high costs of cyclotrons needed to produce the short-lived radionuclides for PET scanning and the need for specially adapted on-site chemical synthesis apparatus to produce the radiopharmaceuticals after radioisotope preparation. Organic radiotracer molecules that will contain a positron-emitting radioisotope cannot be synthesized first and then the radioisotope prepared within them, because bombardment with a cyclotron to prepare the radioisotope destroys any organic carrier for it. Instead, the isotope must be prepared first, then afterward, the chemistry to prepare any organic radiotracer (such as FDG) accomplished very quickly, in the short time before the isotope decays. Few hospitals and universities are capable of maintaining such systems, and most clinical PET is supported by third-party suppliers of radiotracers that can supply many sites simultaneously. This limitation restricts clinical PET primarily to the use of tracers labelled with fluorine-18, which has a half-life of 110 minutes and can be transported a reasonable distance before use, or to rubidium-82 (used as rubidium-82 chloride) with a half-life of 1.27 minutes, which is created in a portable generator and is used for myocardial perfusion studies. Nevertheless, in recent years a few on-site cyclotrons with integrated shielding and "hot labs" (automated chemistry labs that are able to work with radioisotopes) have begun to accompany PET units to remote hospitals. The presence of the small on-site cyclotron promises to expand in the future as the cyclotrons shrink in response to the high cost of isotope transportation to remote PET machines.^[54] In recent years the shortage of PET scans has been alleviated in the US, as rollout of radiopharmacies to supply radioisotopes has grown 30%/year.^[55]

Because the half-life of fluorine-18 is about two hours, the prepared dose of a radiopharmaceutical bearing this radionuclide will undergo multiple half-lives of decay during the working day. This necessitates frequent recalibration of the remaining dose (determination of activity per unit volume) and careful planning with respect to patient scheduling.

History

The concept of emission and transmission tomography was introduced by David E. Kuhl, Luke Chapman and Roy Edwards in the late 1950s. Their work later led to the design and construction of several tomographic instruments at the University of Pennsylvania. In 1975 tomographic imaging techniques were further developed by Michel Ter-Pogossian, Michael E. Phelps, Edward J. Hoffman and others at Washington University School of Medicine.^[56][57]

Work by Gordon Brownell, Charles Burnham and their associates at the Massachusetts General Hospital beginning in the 1950s contributed significantly to the development of PET technology and included the first demonstration of annihilation radiation for medical imaging.^[58] Their innovations, including the use of light pipes and volumetric analysis, have been important in the deployment of PET imaging. In 1961, James Robertson and his associates at Brookhaven National Laboratory built the first single-plane PET scan, nicknamed the "head-shrinker."^[59]

One of the factors most responsible for the acceptance of positron imaging was the development of radiopharmaceuticals. In particular, the development of labeled 2-fluorodeoxy-D-glucose (2FDG) by the Brookhaven group under the direction of Al Wolf and Joanna Fowler was a major factor in expanding the scope of PET imaging.^[60] The compound was first administered to two normal human volunteers by Abass Alavi in August 1976 at the University of Pennsylvania. Brain images obtained with an ordinary (non-PET) nuclear scanner demonstrated the concentration of FDG in that organ. Later, the substance was used in dedicated positron tomographic scanners, to yield the modern procedure.

The logical extension of positron instrumentation was a design using two 2-dimensional arrays. PC-I was the first instrument using this concept and was designed in 1968, completed in 1969 and reported in 1972. The first applications of PC-I in tomographic mode as distinguished from the computed tomographic mode were reported in 1970.^[61] It soon became clear to many of those involved in PET development that a circular or cylindrical array of detectors was the logical next step in PET instrumentation. Although many investigators took this approach, James Robertson^[62] and Zang-Hee Cho^[63] were the first to propose a ring system that has become the prototype of the current shape of PET.

The PET-CT scanner, attributed to Dr. David Townsend and Dr. Ronald Nutt, was named by TIME Magazine as the medical invention of the year in 2000.^[64]

Cost

As of August 2008, Cancer Care Ontario reports that the current average incremental cost to perform a PET scan in the province is Can$1,000–1,200 per scan. This includes the cost of the radiopharmaceutical and a stipend for the physician reading the scan.^[65]
In England, the NHS reference cost (2015-2016) for an adult outpatient PET scan is £798, and £242 for direct access services.^[66]

Quality Control

The overall performance of PET systems can be evaluated by quality control tools such as the Jaszczak phantom.^[67]