This document discusses oncology imaging techniques. It begins by introducing advances in diagnostic imaging that allow visualization of macroscopic disease. It then summarizes key aspects of several major imaging modalities used in oncology, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and conventional radiography. For each modality, it describes the basic imaging principles, contrast mechanisms, applications in oncology, and considerations for clinical interpretation.
2. INTRODUCTION
Advances in diagnostic imaging have increased our ability to
visualize macroscopic disease, referred to as gross tumor
volume (GTV).
Imaging is currently unable to identify microscopic tumor
extension around a primary tumor or occult nodal
involvement.
3. • Radiation treatment planning has undergone considerable
evolution during the past 20 years.
• With conventional planning, the physician conceives of
beam orientations and aperture shapes based on the
interpretation of clinical and diagnostic information,
including three-dimensional (3D) imaging data such as
computed tomography (CT) or magnetic resonance
imaging (MRI).
4. • Radiologic imaging is an integral component in the
management of cancer patients.
• Imaging is utilized in the diagnosis and initial staging of
disease, treatment planning, and posttreatment
Surveillance.
• A general sense of the sensitivity, specificity, and positive
and negative predictive values of an imaging study helps
the clinician assimilate and interpret imaging information
that can be misleading or even contradictory.
5. RADIOGRAPHY
Conventional radiography creates a two-dimensional
grayscale image produced by the differential attenuation of
x-rays that pass through soft tissues of varying density.
Tissues that are very dense, such as bone, will absorb more
x-rays than tissues that are less dense, such as lung.
6. • Radiographs are therefore best suited to detect pathology
when a lesion differs greatly in density from adjacent
structures, such as a soft tissue mass surrounded by
aerated lung or a lytic lesion surrounded by dense bone.
• Radiographs have excellent spatial resolution: the ability to
detect a small object within a given volume. However, they
are suboptimal when there are only subtle differences in
tissue density.
• Therefore, even large lesions can be missed if they are of
similar density to surrounding structures.
7. CT, MRI, and ultrasound (US) generate two-dimensional
cross-sectional images.
The benefits of cross-sectional imaging include visualization
of superimposed structures obscured on planar images,
improved anatomic detail of individual organs and their
precise relationship to adjacent structures, and the ability to
perform multiplanar reconstructions.
Furthermore, some applications provide functional in
addition to morphologic information and can be acquired in
real time, permitting image guidance for procedures.
For these reasons, cross-sectional modalities are the
mainstay of oncologic imaging.
9. COMPUTED TOMOGRAPHY
• CT generates cross-sectional images from the transmission
of radiation through tissue. A patient lies on the scanner
table within a gantry that houses an x-ray generator
opposite multiple rows of detectors, hence the term
multidetector CT (MDCT).
• Current generation scanners (e.g., 64 or 128 MDCT) are
able to acquire high- resolution image data much faster
due to improvements in the number of detectors and
computer processing.
• As the gantry rotates, the detectors measure x-ray
transmission through the rotation, or slice. The patient is
moved through the scanner as the gantry rotates, resulting
in a helical or spiral course at a very thin slice thickness,
typically 0.625 mm.
10. The spatial and temporal data from multiple projections are then
processed by a Fourier transform mechanism generating two-
dimensional axial images.
The thin-slice volume dataset is isotropic, meaning that images can
be reconstructed in orthogonal and oblique planes without a loss
in image quality.
Furthermore, thin-slice acquisition improves contrast resolution
and decreases partial volume artifacts, thereby improving imaging
quality and accuracy.
Images are displayed within a matrix composed of voxels, each
representing a volume of radiodensity that is quantified by a linear
attenuation value called a Hounsfield unit (HU).
11. Each voxel is assigned a HU in the range of –1,000 to 1,000
corresponding to a shade of gray to represent the
attenuation difference between a given material and water.
By convention, air is the least dense material with a HU value
of –1,000, while water has a HU value of 0. Soft tissues have
a range of attenuation with typical HU values as follows: fat
(–120), blood (30), muscle (40), bone (>300).
HU analysis is more accurate than visual assessment of tissue
composition and is particularly useful in characterizing
enhancement postcontrast administration, a feature critical
in the assessment of many solid organ lesions.
12. • Both intravenous (IV) and oral contrast agents may be
utilized to improve spatial resolution. Oral contrast agents
are routinely used for abdominal and pelvic imaging to
distinguish bowel from adjacent organs, lymph nodes, and
tumors.
• The use of an intravascular contrast agent during CT
depends on the study indication, target organ, and patient
status.
• Administration of IV contrast media is required for
thorough assessment of vessels (e.g., aorta, pulmonary
arteries), solid organs (e.g., liver, kidneys), and
characterization of lesion vascularity.
13. • Contrast-enhanced CT is often necessary to detect solid
organ metastases (e.g., liver, adrenal gland, brain).
Contrast is usually not necessary for routine pulmonary
imaging due to the inherent contrast of solid lesions within
a background of aerated lung, although it does improve
the characterization of hilar lymph nodes.
14. • Given that the administration of contrast media can alter
tissue attenuation, the HU value of a lesion or tissue may
differ depending on whether the study was performed
with or without contrast and based on the timing of image
acquisition (e.g., arterial vs. portal venous phase).
• HUs are used during radiation treatment planning dose
calculations; therefore, contrast can affect these
calculations.
• If indicated, the HU within a structure enhanced by
contrast (e.g., the bladder when planning for prostate
cancer treatment) can be set to an alternate value prior to
dose calculations.
15. • A similar phenomenon often occurs when materials with a
high atomic number are within the scanned volume.
• These materials (e.g., dental fillings, hip prostheses) can
cause artifacts that can make it challenging to accurately
segment the image or affect dose calculations. The latter
can also be corrected by setting the HU within the affected
area to the desired value.
16. MAGNETIC RESONANCE IMAGING
• MRI generates cross-sectional images without ionizing radiation.
• MRI utilizes strong magnets, typically 1.5 or 3.0 T for clinical
applications.
• A 3.0 T magnet is 60,000 times greater than the earth’s magnetic field.
• The magnetic field uniformly aligns the nuclei of hydrogen protons
within tissue.
• Applying a radiofrequency (RF) pulse sequence and gradient to the
magnetic field disrupts this alignment and equilibrium.
• When the RF pulse is removed, the protons realign, or relax, within the
field and emit a measurable resonance radio signal. The detected
radio signals, referred to as echoes or spin echoes, are then used to
generate an image.
17. • The most important tissue properties for image generation
are the proton density, the spin-lattice relaxation time (T1)
and the spin-spin relaxation time (T2).
• Different tissues have different proton density and
relaxation times, absorbing and releasing radio wave
energy at different rates, which in part accounts for the
high tissue contrast obtained by MRI.
• Different RF pulse sequences can accentuate different
tissue characteristics by varying parameters such as the
repetition time (TR)—the time between RF pulses in the
sequence, which determines how much time protons have
to realign within the magnetic field—and the echo time
(TE)—the time between the RF pulse and the peak
returning signal.
18. • TR and TE dramatically affect image contrast and determine
which tissue properties are selected.
• T1-weighted images, in which fluid is dark and fat is bright, are
generally good at depicting anatomy;
• T1-weighted images are generated by selecting short TR
(typically ≤800 ms) and short TE values (≤30 ms).
• T2-weighted images, in which fluid is bright and fat is dark, are
fluid-sensitive and can depict areas of pathology;
• T2-weighted images are generated by selecting long TR (≥2,000
ms) and long TE values (≥60 ms).
19. • Gadolinium chelates are the most commonly used MRI
contrast agents, which, like the iodinated CT equivalents,
are confined to the vasculature and do not cross an intact
blood– brain barrier.
• Gadolinium-based contrast media are at increased risk of
developing NSF.
• One of the advantages of MRI over CT is that it can
provide functional in addition to anatomic information.
• This is particularly beneficial in oncologic imaging. MRI
techniques allow for tissue diffusion and perfusion
imaging, quantification of blood flow by velocity phase
encoding, and magnetic resonance proton spectroscopy,
which provides biochemical quantification of tissues.
20. PRECAUTIONS
• MRI has modality-specific artifacts that can limit image
quality. Motion artifact can be problematic with MRI due
to long scan times.
• Chemical shift artifact results in a loss of signal at the
interface of tissues with highly variable contrast
properties.
• MRI is also highly sensitive to magnetic field distortions
that can produce artifacts.
• Patients must be carefully screened to ensure that any
medical devices or surgical hardware are MRI compliant.
21. ULTRASONOGRAPHY
• US is an imaging modality utilizing pulse-echo techniques
rather than radiation to produce an image.
• The US transducer coverts electrical energy into a high-
frequency pulse that is transmitted through tissues.
• The pulse interacts at tissue interfaces, generating a
reflected echo signal that is detected by the transducer.
• The returning sound waves are transformed into a gray
scale image in real time. Image quality is, in large part,
determined by the pulse frequency. High-frequency
transducers
22. • (5–12 MHz) produce high-resolution images but have
limited ability to penetrate. Therefore, they are best suited
to imaging superficial structures such as the breast or
thyroid.
• Low frequency transducers (1–3.5 MHz) generate lower
quality images but have better tissue penetration and are
most often used for imaging abdominal and pelvic organs.
• The degree to which tissues are visualized by US is called
echogenicity. Fat is highly echogenic (bright), whereas
fluid-containing structures, such as simple cysts, are
anechoic (dark).
23. COLOR DOPPLER
• Color Doppler US is an important adjunct to conventional
gray-scale sonography.
• The Doppler effect is a change in frequency of returning
sound waves reflected by a moving object, such as flowing
blood.
• If blood flows away from the transducer, the echo
frequency decreases; whereas if blood flows toward the
transducer, the echo frequency increases.
• The change in frequency is directly proportional to the
flow velocity and produces a color overlay in areas of flow
on the standard gray-scale US image.
• Color Doppler US is useful in characterizing blood flow
within lesions and assisting in image-guided procedures.
24. ENDOSCOPIC ULTRASOUND
• Endoscopic ultrasound (EUS) was introduced in the early 1980 s and
has become a tool important in oncologic staging.
• It allows for high-resolution images of internal structures not typically
accessible by high-frequency transducers by passing the probe
through bowel or airways.
• It is most widely applied in the setting of gastrointestinal (GI)
malignancies, especially esophageal and rectal carcinomas.
• A 5 to 12 MHz transducer can readily identify five of the layers of the
gastrointestinal tract. Higher frequency transducers can identify
additional layers, such as the muscularis mucosa and lamina propria of
the esophagus, which has important staging implications.
25. • EUS is also utilized for characterization and image-guided sampling of
regional lymph nodes in GI or bronchopulmonary disease. The ability
of EUS to predict the tumor (T) stage is generally superior to its ability
to predict the node (N) stage.
• Suspicious lymph nodes are typically round, >10 mm in short axis,
have distinct margins, and are typically hypoechoic. If all four features
are present, the likelihood of malignancy is 80% to 100%. There is,
however, considerable overlap between benign and malignant
features of lymph nodes on EUS in addition to wide inter-observer
variability.
• Tissue sampling is therefore recommended for accurate staging. When
describing clinical T and N staging by EUS, the prefix u should be
utilized (e.g., uT3N1).
26. AXIAL ENDOSCOPIC ULTRASOUND IMAGE (RIGHT) AND HISTOLOGIC SPECIMEN (LEFT) FROM A NORMAL ESOPHAGUS. THE ENDOSCOPIC
ULTRASOUND
LAYERS AND HISTOLOGIC LAYERS OF THE ESOPHAGUS ARE CORRELATED (SEE TABLE 30.3). (ENDOSCOPIC ULTRASOUND IMAGE COURTESY OF
DR. F RANK GRESS. H ISTOLOGIC
IMAGE COURTESY OF DR. DANIEL GOODENOUGH.)
28. INTRODUCTION
• Although radiographic and cross-sectional studies provide important anatomic
information regarding pathologic processes, nuclear radiology provides physiologic
information based on the distribution of an injected or ingested
radiopharmaceutical.
• Radiopharmaceuticals consist of a radioactive substrate (radionuclide,
radioisotope, or radiotracer) that is coupled with a physiologically active compound
or analog. For example, technetium-99 m is a radioisotope that is coupled to
pertechnetate, an iodine analog, which can enter thyroid follicular cells.
• The timing of imaging depends on the kinetics of absorption, metabolism, and half-
life of the radionuclide. Gamma rays emitted by nuclear decay of the radionuclide
are then detected using a γ-camera corresponding to radiotracer activity that is
described in terms of uptake.
• Indium-111 capromab pendetide (ProstaScint) can be utilized for prostate cancer
and gallium-67 can be used for lymphomas.
29. POSITRON EMISSION TOMOGRAPHY
• Although several radionuclides for PET are available, the most
common is 18-fluorodeoxyglucose (FDG).
• FDG is a glucose analog that concentrates in areas of high metabolic
activity. Tumor cells are often highly metabolic, with rapid cell division
and an increased number of glucose transporters.
• However, FDG uptake is not specific for malignancy and accumulates
in any cell with increased metabolic activity, including myocardium,
gastric mucosa, brain tissue, thyroid, and salivary glands, which limits
evaluation of these organs. 2
30. • Furthermore, FDG tracer is excreted within the urinary system;
therefore, activity within the kidneys, collecting system, and bladder
can obscure malignancy of these structures.
• Notwithstanding these limitations, PET-CT has become the preferred
imaging modality for clinical staging, facilitating the characterization of
benign versus malignant pathology, detecting sites of unsuspected
disease, identifying optimal sites for tissue sampling, assessing
treatment response, and monitoring for recurrence for multiple
malignancies.
• PET-CT combines the physiologic assessment of PET with the anatomic
assessment of CT, resulting in improved diagnostic accuracy.
31. • Patients must fast for 4 to 6 hours prior to scanning in order to limit metabolic
activity within the GI tract.
• Blood glucose levels should be well controlled (<150 mg/dL) to limit glucose
receptor competition with FDG, as high glucose levels can result in a false-
negative scan.
• Speech and motion should be restricted to minimize muscle uptake, which
could obscure pathology.
• Approximately 1 hour following FDG administration, a CT scan is performed
immediately followed by PET imaging, which can take up to 60 minutes.
• CT and PET datasets are then reconstructed in separate axial, coronal, and
sagittal series as well as fused PET-CT images.
32. • FDG uptake is nonspecific, localizing to any tissue with increased
metabolic activity. Although most malignant tumors are
hypermetabolic relative to normal tissues, non-malignant processes
also concentrate FDG, including foci of infection, inflammation, and
benign neoplasms.
• FDG uptake is quantified by the standard uptake value (SUV). Most
malignant tumors have a maximum SUV >2.5, while physiologic uptake
is typically <2.5. SUVs are not absolute and can be affected by the
timing of imaging, improper attenuation correction, partial volume
affects, patient weight, FDG dose, and factors affecting FDG uptake.
• Clinical studies to date have documented that under such uniform
conditions, changes in SUV have prognostic value, indicating that most
tumors responding to therapy show a 20% to 40% decrease in SUV
early in course of treatment.
33. BONE SCINTIGRAPHY
• Normal bone undergoes continuous remodeling, maintaining a delicate
balance between osteoblastic and osteoclastic activity.
• Most bone metastases originate as intramedullary lesions, having gained
access to the bone through the vasculature.
• As the lesions enlarge, reactive osteoblastic and osteoclastic changes result in
characteristic radiographic changes indicative of bone metastases (sclerotic,
lytic, or mixed lesions).
• Rapidly growing metastases tend to produce lytic lesions, while more slowly
growing metastases typically produce sclerotic (or blastic) lesions.
• Metastases from multiple myeloma, thyroid cancer, and renal cell carcinoma
are predominantly lytic, while blastic lesions are associated with breast and
prostate cancers.
• The primary utility of bone scintigraphy in oncologic imaging is the detection
of osseous metastatic disease.
34. • Bone scintigraphy or bone scan imaging utilizes radiopharmaceuticals composed of
bisphosphonates; the most common of which is the radionuclide technetium-99 m
methylene diphosphonate (99mTc-MDP).
• 99mTc-MDP localizes to areas of new bone mineralization, which occurs in a wide
array of bone pathology and is therefore highly sensitive to osseous disease, but is
not very specific.
• Although a 30% to 50% reduction in bone density must occur before bone
metastases are detected on radiographs, as little as 5% to 10% change is required
to detect such on a bone scan.
• Furthermore, bone scans are relatively inexpensive, convenient, and visualize the
entire skeleton, including sites that are difficult to assess on plain films (e.g., ribs,
sternum, scapula, sacrum). Reported sensitivities range from 62% to 100% with
similar specificity rates (78% to 100%).18
35. • Two primary patterns of radiotracer activity can be associated with
malignancy: increased or decreased activity.
• Increased uptake occurs in areas of increased blood flow and
osteoblastic activity; this is a common finding in metabolically active
tumors and small sclerotic metastatic foci.
• Decreased radiotracer activity occurs as a “cold” area on bone scan
and is associated with lytic bone disease and aggressive tumors that
outgrow their blood supply.
• Rapidly progressing and purely lytic disease are the main causes of
false-negative findings on bone scintigraphy, while false-positive
findings can be related to trauma, healing, benign bone tumors, or
arthritic changes
36. • Tumor response may cause a “flare phenomenon,”
resulting from increased activity secondary to new
osteoblastic activity concomitant with new bone
formation. This may be falsely attributed to progressive
disease.
• Similarly, lytic lesions that were previously “cold” on bone
scan can transform into “hot” spots (areas of uptake) after
treatment.
• Second, rapidly progressive disease with overwhelming
bone destruction without new bone formation can be
misinterpreted as stable or responding disease on bone
scan.
37. Choose the most appropriate
imaging modality is the key for
accurate, effective diagnosis and
treatment