1.1.4 PET & Ultrasound Imaging

"Functional imaging allows us to see the activity of life, not just the structure of the body." — A New Era of Medical Imaging

In previous chapters, we learned about three major anatomical imaging technologies: CT, MRI, and X-ray. Now, let's explore two unique imaging modalities: PET (Positron Emission Tomography) and Ultrasound Imaging. PET represents functional imaging, capable of displaying tissue metabolic activity; ultrasound is the exemplar of real-time imaging—radiation-free, portable, and economical. These two technologies form a perfect complement to the anatomical imaging technologies discussed earlier.

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🔬 Part 1: PET (Positron Emission Tomography)

From Antimatter to Medical Imaging

Discovery of the Positron: Antimatter's First Appearance

In 1932, American physicist Carl Anderson at Caltech, while studying cosmic rays, observed a peculiar particle track in a cloud chamber: it had the same mass as an electron but opposite charge. This was the positron, the first antimatter particle discovered by humans. Anderson received the 1936 Nobel Prize in Physics for this discovery.

At the time, no one imagined that this seemingly pure physics discovery would completely transform medical diagnosis decades later.

💡 What is Antimatter?

Antimatter is the "mirror image" of normal matter: the positron is the antiparticle of the electron, and the antiproton is the antiparticle of the proton. When matter and antimatter meet, annihilation occurs, with mass completely converting to energy, producing high-energy photons. This process follows Einstein's mass-energy equation E=mc². PET imaging utilizes precisely this physical phenomenon.

Radioactive Tracers: Tracking Life's Footprints

In 1943, Hungarian chemist George de Hevesy received the Nobel Prize in Chemistry for developing radioactive tracer technology. His pioneering work demonstrated that radioactive isotopes could be used to label substances and then track their metabolic processes in living organisms.

This idea laid the foundation for functional imaging: if we could label glucose with radioactive isotopes, we could see energy consumption in different parts of the body.

Birth of the First PET Scanner

In 1973, at Washington University School of Medicine, physicists Michael Phelps and Edward Hoffman, under the guidance of Michel Ter-Pogossian, built the world's first PET scanner—PETT I (Positron Emission Transaxial Tomograph).

This device had only one detector ring and required hours for a single scan, but it proved the feasibility of PET imaging.

FDG: The "Fuel" of PET Imaging

In 1976, at Brookhaven National Laboratory in the United States, Tatsuo Ido, Al Wolf, and Joanna Fowler successfully synthesized ¹⁸F-fluorodeoxyglucose (FDG).

FDG is a glucose analog that is taken up by cells but not completely metabolized, thus accumulating in metabolically active tissues. Since cancer cells' metabolic rate is typically several times that of normal cells, FDG-PET became a powerful tool for tumor diagnosis.

🎯 Why Do Cancer Cells "Love" Glucose?

This is called the Warburg effect: even under aerobic conditions, cancer cells tend to obtain energy through glycolysis rather than the more efficient aerobic respiration. This causes cancer cells to take up glucose at rates far higher than normal cells, enabling FDG-PET to "light up" tumors.

PET Imaging Principle: Capturing the Glow of Annihilation

Positron Annihilation: A Microscopic "Firework"

The core of PET imaging is the positron annihilation process:

1. Radioactive Tracer Injection: Inject a tracer (such as FDG) labeled with a positron-emitting nuclide (such as ¹⁸F) into the patient
2. Positron Emission: The radioactive nuclide decays, releasing positrons
3. Positron Annihilation: The positron travels a very short distance in tissue (about 1-2 millimeters) before encountering an electron and annihilating
4. Photon Pair Production: Annihilation produces two γ photons with energy of 511 keV, flying out in opposite directions at 180 degrees
5. Coincidence Detection: The PET scanner's detector ring simultaneously detects this photon pair, determining the location of annihilation

Coincidence Detection Technology: Timing is Everything

PET scanners use coincidence detection technology:

• Only photon pairs detected simultaneously by two opposing detectors within an extremely short time window (typically <10 nanoseconds) are considered to come from the same annihilation event
• The line connecting the two detectors is called the Line of Response (LOR)
• Through reconstruction of millions of LORs, a three-dimensional distribution image of the tracer in the body can be obtained

Commonly Used Radioactive Tracers

Tracer	Half-life	Labeling Nuclide	Main Applications
¹⁸F-FDG	110 minutes	¹⁸F	Tumors, heart, brain metabolism
¹¹C-Methionine	20 minutes	¹¹C	Brain tumors, protein synthesis
¹³N-Ammonia	10 minutes	¹³N	Myocardial perfusion
¹⁵O-Water	2 minutes	¹⁵O	Cerebral blood flow
⁶⁸Ga-PSMA	68 minutes	⁶⁸Ga	Prostate cancer

⚠️ Safety of Radioactive Tracers

Although PET uses radioactive materials, the radiation dose is controllable:

• A single FDG-PET scan has an effective dose of about 5-7 mSv, equivalent to 1-2 abdominal CT scans
• Tracers have very short half-lives (¹⁸F is 110 minutes), decaying rapidly
• Tracer amounts are extremely small (typically <10 milligrams), producing no pharmacological effects
• Pregnant and lactating women require special risk-benefit assessment

PET Fusion with CT/MRI: 1+1>2

PET images alone only show functional information, lacking anatomical detail. In 2000, David Townsend's team developed the first commercial PET-CT scanner, named "Medical Invention of the Year 2000" by Time magazine.

Advantages of PET-CT:

• CT provides precise anatomical localization
• CT data used for PET image attenuation correction, improving quantitative accuracy
• One scan simultaneously obtains functional and anatomical information
• Scan time reduced from 2 hours to 30 minutes

In the 2010s, PET-MRI began clinical application, combining MRI's excellent soft tissue contrast with PET's functional imaging capability, particularly suitable for brain and pelvic imaging.

Modern PET-CT scanner, perfectly integrating functional and anatomical imaging

Evolution of PET Technology

Era	Milestone Events	Key Technologies	Scan Time	Main Applications
1970s-1980s	Proof of concept stage	Single-ring detector, BGO crystal	2-4 hours	Brain metabolism research
	1973: First PET scanner (PETT I)
	1976: FDG synthesis successful
1990s-2000s	Clinical application popularization	Multi-ring detector, whole-body scanning	30-60 minutes	Tumor diagnosis and staging
	FDG-PET became tumor diagnosis standard
	1998: FDA approved FDG for clinical use
2000s	Fusion imaging era	PET-CT, LSO crystal	15-30 minutes	Tumors, heart, neurology
	2000: First commercial PET-CT
	Time-of-flight (TOF) technology
2010s	Multimodal & precision imaging	PET-MRI, digital PET	10-20 minutes	Precision medicine, early diagnosis
	2010: First PET-MRI
	Fully digital PET detectors
2020s-present	Whole-body & ultra-fast imaging	Whole-body PET, AI reconstruction	<10 minutes	Whole-body tumor screening
	Long Axial Field of View (LAFOV) PET
	Ultra-sensitive detectors

Key Technology Breakthroughs

Technology Category	Technology Name	Time	Core Contribution	Performance Improvement
Detector	BGO crystal	1980s	High density, high stopping power	Improved detection efficiency
Detector	LSO/LYSO crystal	2000s	Faster decay time	Improved count rate, better image quality
Detector	Digital SiPM	2010s	Fully digital, high sensitivity	Improved time resolution, reduced dose
Imaging Technology	Time-of-Flight (TOF)	2000s	Utilize photon arrival time difference	Improved SNR 30-40%
Imaging Technology	Point Spread Function (PSF) reconstruction	2000s	Compensate system response	Improved spatial resolution
Fusion Imaging	PET-CT	2000	Anatomy + function	Improved diagnostic accuracy, reduced scan time
Fusion Imaging	PET-MRI	2010	Soft tissue contrast + function	Reduced radiation, improved soft tissue resolution
AI Assistance	Deep learning reconstruction	2010s	Denoising, accelerated imaging	Reduced dose 50%, shortened scan time

🚀 Whole-Body PET: One Scan, Full Body View

In 2018, a research team at UC Davis developed the EXPLORER whole-body PET scanner with an axial field of view of 2 meters, capable of covering the entire body in one scan. This Long Axial Field of View (LAFOV) PET offers advantages:

• 40x sensitivity improvement
• Scan time reduced from 20 minutes to 1 minute
• 40% radiation dose reduction
• Can perform whole-body dynamic imaging, observing real-time tracer distribution throughout the body

This opens new possibilities for whole-body tumor screening and systemic disease diagnosis.

Clinical Significance of PET Technology

Application Area	Typical Applications	Clinical Value	Common Tracers
Oncology	Tumor diagnosis and staging	Early detection, accurate staging, metastasis assessment	¹⁸F-FDG
	Treatment response evaluation	Early assessment of treatment response, adjust regimen	¹⁸F-FDG
	Radiation therapy planning	Precise tumor boundary localization	¹⁸F-FDG, ¹¹C-Methionine
Neurology	Alzheimer's disease	Early diagnosis, differential diagnosis	¹⁸F-FDG, amyloid tracers
	Epilepsy	Epileptogenic focus localization	¹⁸F-FDG
	Parkinson's disease	Dopamine system assessment	¹⁸F-DOPA
Cardiovascular	Myocardial viability assessment	Determine if myocardial damage is reversible	¹⁸F-FDG, ¹³N-Ammonia
	Myocardial perfusion	Assess coronary artery disease	¹³N-Ammonia, ⁸²Rb
Infection/Inflammation	Infection focus localization	Etiological diagnosis of fever of unknown origin	¹⁸F-FDG

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🔊 Part 2: Ultrasound Imaging

From Sonar to Medical Imaging

Early Applications of Ultrasound

Ultrasound waves (frequency >20 kHz, beyond human hearing range) were first applied during World War I in sonar (SONAR) technology for detecting submarines. After the war, ultrasound technology was used for industrial flaw detection, checking for cracks inside metals.

But applying ultrasound to medical diagnosis was a much greater challenge: human tissue is far more complex than metal, and real-time imaging is required.

Pioneers of Medical Ultrasound

In 1942, Austrian neurologist Karl Dussik first attempted to use ultrasound transmission imaging to diagnose brain tumors. Although this attempt was unsuccessful (ultrasound cannot penetrate the skull), it opened the exploration of medical ultrasound.

In 1958, Ian Donald, an obstetrician at the University of Glasgow in Scotland, published a landmark paper demonstrating ultrasound applications in obstetric diagnosis. He collaborated with engineer Tom Brown to improve industrial flaw detection equipment, successfully using ultrasound to observe fetuses and ovarian cysts.

👶 Ultrasound Transformed Obstetrics

Before ultrasound, doctors could only assess fetal condition through palpation and auscultation, with many abnormalities undetectable before birth. Ultrasound completely changed this:

• Confirm pregnancy and number of fetuses
• Assess fetal growth and development
• Detect fetal malformations
• Monitor placental position
• Guide procedures like amniocentesis

Ultrasound made prenatal diagnosis possible, greatly reducing maternal and neonatal mortality.

Real-Time Ultrasound Breakthrough

Early ultrasound devices could only produce static images, requiring manual scanning and recording. In the 1970s, with advances in electronics, real-time B-mode ultrasound emerged, capable of producing dozens of frames per second, enabling dynamic observation.

This made ultrasound a true "real-time imaging" tool, capable of observing heartbeats, blood flow, fetal movement, and other dynamic processes.

Ultrasound Imaging Principle: The Echo of Sound Waves

Nature of Ultrasound

Ultrasound is a mechanical wave that requires a medium for propagation and cannot travel in a vacuum. Medical ultrasound frequencies typically range from 1-20 MHz:

• Low frequency (1-5 MHz): Strong penetration, used for deep organs (such as abdomen)
• High frequency (7-20 MHz): High resolution, used for superficial structures (such as thyroid, vessels)

Ultrasound Generation: Piezoelectric Effect

The core of an ultrasound transducer is a piezoelectric crystal (such as lead zirconate titanate, PZT):

• Direct piezoelectric effect: Apply voltage → crystal vibrates → produces ultrasound
• Inverse piezoelectric effect: Ultrasound → crystal vibrates → produces voltage

The same crystal serves as both transmitter and receiver, alternately emitting and receiving ultrasound.

Medical ultrasound linear array probe, containing multiple piezoelectric crystal arrays

Ultrasound Interactions with Tissue

When ultrasound propagates through tissue, several phenomena occur:

1. Reflection

• Occurs at interfaces between different tissues
• Reflection intensity depends on acoustic impedance difference
• This is the main source of ultrasound imaging information

2. Scattering

• Occurs when encountering structures smaller than wavelength
• Produces tissue "texture" information

3. Attenuation

• Ultrasound energy gradually weakens with depth
• Attenuation degree proportional to frequency
• Limits ultrasound penetration depth

4. Refraction

• Ultrasound changes direction at interfaces
• May produce artifacts

Ultrasound Imaging Modes

Mode	Full Name	Display Method	Main Applications
A-mode	Amplitude mode	One-dimensional waveform	Ophthalmology (eye axis length measurement)
B-mode	Brightness mode	Two-dimensional grayscale image	Most common, abdomen, obstetrics, heart, etc.
M-mode	Motion mode	Time-depth curve	Cardiac valve motion, fetal heart monitoring
Color Doppler	Color Doppler	Color blood flow overlaid on B-mode image	Vessels, cardiac blood flow
Spectral Doppler	Spectral Doppler	Blood flow velocity-time curve	Hemodynamic assessment
Power Doppler	Power Doppler	Display blood flow energy distribution	Low-velocity flow, tumor vessels

Doppler Effect: Seeing Blood Flow

Doppler effect: When a sound source and observer are in relative motion, the observed frequency changes. In medical ultrasound:

• Blood flowing toward probe → frequency increases (typically displayed as red)
• Blood flowing away from probe → frequency decreases (typically displayed as blue)

By measuring frequency change, blood flow velocity can be calculated:

$$v=\frac{c\cdot \mathrm{\Delta }f}{2f_0\cos \theta }$$

Where: v is blood flow velocity, c is sound speed, Δf is frequency change, f₀ is transmitted frequency, θ is angle between ultrasound beam and blood flow direction.

💡 Why Does Ultrasound Examination Require Coupling Gel?

Air's acoustic impedance differs greatly from human tissue, causing ultrasound to almost completely reflect at the air-skin interface, unable to enter the body. Coupling gel (typically water-based gel) eliminates air between the probe and skin, ensuring ultrasound can effectively enter the body. This is like using immersion oil in optical microscopy to improve resolution.

Evolution of Ultrasound Technology

Era	Milestone Events	Key Technologies	Image Quality	Main Applications
1940s-1960s	Exploration stage	A-mode ultrasound, contact scanning	One-dimensional waveform	Brain midline, ophthalmology
	1942: Dussik attempted brain ultrasound
	1958: Ian Donald obstetric ultrasound
1970s-1980s	Real-time imaging era	Real-time B-mode, linear/convex array probes	Grayscale images	Obstetrics, abdomen, heart
	1970s: Real-time B-mode emerged
	Grayscale imaging technology
1980s-1990s	Color Doppler era	Color Doppler, spectral Doppler	Color blood flow images	Vessels, heart, obstetrics
	1980s: Color Doppler imaging
	Digital ultrasound systems
1990s-2000s	3D imaging era	3D/4D ultrasound, harmonic imaging	Three-dimensional images	Obstetrics (fetal face), heart
	1990s: 3D ultrasound reconstruction
	Tissue Harmonic Imaging (THI)
2000s-2010s	Functional imaging era	Contrast-enhanced ultrasound, elastography	Functional information	Tumors, liver, breast
	2000s: Microbubble contrast agents
	Shear wave elastography
2010s-present	Intelligence era	AI-assisted diagnosis, portable ultrasound	Intelligent optimization	General applications, telemedicine
	Deep learning image enhancement
	Handheld ultrasound devices

Key Technology Breakthroughs

Technology Category	Technology Name	Time	Core Contribution	Clinical Value
Imaging Technology	Real-time B-mode	1970s	Dynamic observation	Enable cardiac, fetal dynamic imaging
Imaging Technology	Color Doppler	1980s	Blood flow visualization	Vascular disease diagnosis, cardiac valve assessment
Imaging Technology	Tissue Harmonic Imaging (THI)	1990s	Utilize second harmonic	Improve image contrast and resolution
Imaging Technology	3D/4D ultrasound	1990s	Three-dimensional imaging	Fetal malformation diagnosis, cardiac structure assessment
Contrast Technology	Contrast-Enhanced Ultrasound (CEUS)	2000s	Microbubble contrast agents	Tumor blood supply assessment, liver lesion differentiation
Functional Imaging	Elastography	2000s	Tissue stiffness measurement	Liver fibrosis assessment, breast mass differentiation
Probe Technology	Phased array probe	1980s	Electronic scanning	Cardiac imaging, transcranial Doppler
AI Assistance	Deep learning enhancement	2010s	Automatic measurement, lesion detection	Improve diagnostic efficiency and accuracy

🎯 Ultrasound Elastography: "Touching" Tissue Stiffness

Traditionally, doctors assess tissue stiffness (such as whether a mass is hard or soft) through palpation. Ultrasound elastography digitizes this palpation:

• Strain elastography: Manually compress tissue, observe deformation degree
• Shear wave elastography: Emit "push pulse" to generate shear waves, measure propagation velocity to quantitatively assess stiffness

This technology is particularly useful in liver fibrosis assessment, non-invasively replacing liver biopsy.

Clinical Significance of Ultrasound Technology

Application Area	Typical Applications	Clinical Value	Technical Features
Obstetrics	Fetal monitoring	Assess fetal growth, detect malformations	Real-time, no radiation, repeatable
	Prenatal diagnosis	Down syndrome screening, structural abnormalities	3D/4D imaging
Cardiology	Echocardiography	Assess cardiac structure and function	Real-time, Doppler blood flow
	Valvular disease	Diagnose valve stenosis or regurgitation	Color Doppler
Abdomen	Liver, gallbladder, pancreas, spleen	Stones, tumors, inflammation diagnosis	No radiation, convenient
	Liver fibrosis	Non-invasive assessment of cirrhosis degree	Elastography
Vascular	Carotid artery	Atherosclerosis, stenosis assessment	Doppler blood flow
	Deep vein thrombosis	DVT diagnosis	Real-time compression test
Breast	Mass differentiation	Benign-malignant differentiation	Elastography, contrast
Interventional Guidance	Biopsy	Real-time needle guidance	Real-time imaging
	Treatment monitoring	Ablation treatment monitoring	Real-time, no radiation

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🔄 Part 3: Comparison and Complementarity of PET and Ultrasound

Although PET and ultrasound are completely different imaging technologies, they form an interesting complementary relationship in clinical practice:

Feature	PET	Ultrasound
Imaging Principle	Positron annihilation, γ-ray detection	Ultrasound wave reflection
Information Type	Functional imaging (metabolism, receptor distribution)	Anatomical imaging (structure, blood flow)
Temporal Resolution	Low (minute-level)	Extremely high (real-time, millisecond-level)
Spatial Resolution	Medium (4-6 mm)	High (0.1-1 mm)
Penetration Depth	Whole body	Limited (<20 cm)
Radiation	Yes (5-7 mSv)	None
Contrast Agent	Radioactive tracers	Microbubble contrast agents (optional)
Cost	Very high	Low
Portability	None (large equipment)	High (portable)
Operator Dependence	Low	High
Typical Applications	Tumor staging, treatment response, neurodegenerative diseases	Obstetrics, heart, abdomen, vessels, interventional guidance
Advantages	Whole-body imaging, early metabolic changes, quantitative analysis	Real-time, no radiation, portable, economical, repeatable
Limitations	Radiation, high cost, low temporal resolution, requires cyclotron	Operator dependent, limited penetration depth, bone and gas interference

💡 The Power of Complementarity

PET and ultrasound are often used complementarily in clinical practice:

• Tumor Diagnosis: PET detects whole-body metastases, ultrasound guides biopsy
• Treatment Response: PET assesses metabolic response, ultrasound monitors tumor size changes
• Cardiac Disease: PET assesses myocardial viability, ultrasound assesses cardiac structure and function
• Obstetrics: Ultrasound is the first choice for prenatal examination (no radiation), PET requires careful risk-benefit assessment for pregnant women with tumors

Each technology has its strengths, and reasonable selection and combined use can provide the best diagnostic approach for patients.

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💡 Key Takeaways

1. Historical Significance of PET: From the discovery of the positron in 1932, to the first PET scanner in 1973, to the synthesis of FDG in 1976, PET pioneered a new era of functional imaging, enabling us to "see" tissue metabolic activity.

2. PET Imaging Principle: Utilizes 511 keV photon pairs produced by positron annihilation, reconstructing three-dimensional tracer distribution through coincidence detection technology. FDG-PET exploits cancer cells' high metabolic characteristics, becoming a powerful tool for tumor diagnosis.

3. PET Technology Evolution: From early single-ring detectors to modern PET-CT and PET-MRI fusion imaging, from hours-long scans to 10-minute whole-body imaging, PET technology continues to advance. Whole-body PET (LAFOV) represents the latest development direction.

4. Historical Significance of Ultrasound: From Dussik's early attempts in 1942 to Ian Donald's successful obstetric application in 1958, ultrasound became one of the most widely used medical imaging technologies, completely transforming obstetrics.

5. Ultrasound Imaging Principle: Utilizes ultrasound wave reflection at different tissue interfaces, achieving transmission and reception through the piezoelectric effect. The Doppler effect enables blood flow visualization. Ultrasound is the only real-time, radiation-free imaging technology.

6. Ultrasound Technology Evolution: From A-mode ultrasound to real-time B-mode, from grayscale imaging to color Doppler, from 2D to 3D/4D, from pure anatomical imaging to functional imaging (elastography, contrast), ultrasound technology continues to innovate.

7. Complementarity of PET and Ultrasound: PET provides whole-body functional information, suitable for tumor staging and treatment response assessment; ultrasound provides real-time anatomical information, suitable for dynamic observation and interventional guidance. Combined use provides more comprehensive diagnostic information.

8. Safety Considerations: PET uses radioactive tracers with some radiation dose (5-7 mSv), but within acceptable range; ultrasound is completely radiation-free, making it the first choice for pregnant women and children.

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💡 Next Steps

Now you understand four major medical imaging modalities (CT, MRI, X-ray, PET) and one special imaging technology (ultrasound). In Chapter 3, we will delve into reconstruction algorithms and image enhancement techniques for these images. In Chapter 2, we will learn about medical image data format standards (such as DICOM) and commonly used open-source tools.