A. Overview of Methods [1,2]

1. Plain Radiography - X-rays
2. Computed Tomographic Scans (CT)
3. Magnetic Resonance Imaging (MRI)
4. Positron Emission Tomography (PET)
5. Single-Proton Emission Tomography (SPECT)
6. Nuclear Medicine Scans
7. Ultrasonography

B. Plain Radiographs (X-Rays)

1. X-irradiation is relatively high energy
2. Passage through tissue attenuates X-rays
3. The intensity of exiting radiation is measured by sensitive films
4. Administration of contrast material increases X-ray attenuation
   1. Heavy elements are used in most cases (barium, iodine)
   2. Non-ionic contrast agents are also available
5. Projection of three dimensional structures onto two dimensional film
6. Therefore, depth dimension is collapsed to a single image
7. Advantages
   1. Rapid study times
   2. Widespread availability
   3. Relatively inexpensive
8. Variations on standard X-rays with contrast are commonly employed
   1. Barium contrast for upper and lower gastrointestinal tract visualization
   2. Intravenous (iodinated) agents for angiography (such as IV pyelogram)

C. Computed Tomography (CT) [5]

1. Uses X-rays but exiting radiation is measured from multiple different directions
   1. Source of X-rays rotates around patient
   2. Motorized table moves patient through CT imaging system
   3. In axial CT (usually for head scan), table is stationary during rotation of X-ray emitter
   4. In helical (also called spiral) CT, for body scans, table moves continuously as emitter moves
   5. Detectors measure degree of X-ray attenuation
   6. Computers integrate information into cross-sectional data
   7. Significantly more (~50X) radiation than standard X-ray for lungs
2. Intravenous contrast medium with CT permits detection of blood leakage
3. CT angiography is a newer variation permitting vessel
4. Advantages of CT include:
   1. Widespread availability
   2. Short times for studies (good in emergency situations)
   3. Sensitive detection of calcification
   4. Detection of acute hemorrhage
   5. Extremely good for imaging bone anatomy
   6. Particularly good modality for imaging sinuses
   7. Cost is about 50% of that of MRI
   8. Superior accuracy to ultrasound for appendicitis [12]
5. CT Disadvantages include:
   1. Relatively high dose of ionizing (X-) radiation
   2. Relatively insensitive to tissue pathophysiologic changes
   3. Relatively less sensitive for detection of occipital and temporal brain lesions
   4. This is due to beam hardening artifacts which occur in base of skull region
   5. All images produced with conventional CT are in cross-sectional plane
6. Spiral (Helical) Computed Tomography (CT) [3,4]
   1. Spiral CT produces volumetric two-dimensional image of (usually) lung
   2. This is accomplished by giving IV contrast agent and rotating detector around the patient
   3. Total acquisition time is <30 seconds
   4. PE appears as a filling defect that may be central, eccentric or mural
   5. The embolism may completely or partially occlude the vessel
   6. Test is very quick, but costly, requires IV contrast and careful interpretation
   7. Reported sensitivity 53-100%, specificity 81-100%
   8. Negative predictive value in patients with suspected PE and nondiagnostic V/Q scan 96% [4]
   9. Screening persons at high risk for lung cancer with spiral CT leads to early detection and apparent reduction in mortality [20]
7. Multidetector-row CT and D-dimer testing can be used without ultrasound to rule out PE [17]
8. Multislice CT is highly accurate for suspected obstructive coronary arter disease [18]
9. CT Colonography [16]
   1. Three-dimensional reconstruction of colonic images
   2. High specificity 92-97%
   3. Sensitivity for polyps 48% for <6mm, 70% for 6-9mm, 85% for >9mm
   4. Not yet routinely used due to highly variable sensitivity

D. Magnetic Resonance Imaging (MRI)

1. Technological Basis
   1. Patient is placed in a strong magnetic field (usually 1-2 Tesla)
   2. All hydrogen nuclei within body tissue are aligned in same direction
   3. Radiofrequency (RF) pulse is applied to tissue to push hydrogen nuclei out of alignment
   4. The RF pulse is then stopped, and the hydrogen nuclei return to their aligned direction
   5. The parameters of relaxation are measured
2. Relaxation Times
   1. The time it takes the nuclei to realign with magnetic field is the T1 time
   2. The time it takes the nuclei to lose energy that keeps them aligned with the original magnetic field is the T2 time
   3. T2 is always shorter than T1
3. Brightness of MRI Images
   1. Concentration of hydrogen nuclei in tissue (proton density or spin density)
   2. Weight given to T1 and T2 components of the image
   3. The T1 or T2 weights depend on the radiofrequency pulse sequences
   4. On T1 weighted images, tissues with short T1 appear brighter than those with long T1
   5. On T2 weighted images, tissues with long T2 appear brighter than those with short T2
   6. On Proton Density Images (mixed T1 and T2 effects), CSF and brain tissue is distinct
   7. Gradient recalled echo (GRE) MRI is more sensitive to parenchymal brain hemorrhage than other MRI modalities or CT [13]
4. T1 Bright Images
   1. Primarily tissues high in fat (lipid) content
   2. T1 is highly dependent on the characteristics of the magnetic field
5. T2 Bright Images
   1. Primarily tissues high in water content
   2. Signal highly dependent on interactions between hydrogen nuclei and macromolecules
6. Gadolinium (Gad) Enhancement
   1. Gadolinium deithylenetriamine pentaacetic acid (Gd-DPTA) contrast agent for MRI
   2. Various similar brands: Magnavist®, MultiHance®, Omniscan®, OptiMARK®, ProHance®
   3. Enhances relaxation of hydrogen nuclei
   4. Gad has more effect on T1 relaxation than on T2 relaxation
   5. Hyperenhancement of contrast agent in nonviable myocardium for ventricular analysis [6]
   6. Single case reports of acute renal failure with Gad
7. Nephrogenic Systemic Fibrosis (NSF) [21,24,25]
   1. Previously called nephrogenic fibrosing dermopathy
   2. Only reported in some patients with renal failure exposed to Gad
   3. NSF is a fibrotic disease similar to scleroderma with Indurated plaques, hyperpigmentation, sclerodactyly
   4. Painful tightening of skin with tethering to underlying fascia
   5. Usually begins on hands and feet and extends proximally
   6. Woody induration, brawny hyperpigmentation, peau d'orange changes of skin
   7. Contractures of elbow, finger, knee and ankle; facial involvement not reported
   8. Rare condition primarily in patients on dialysis (but some transplant or acute renal failure)
   9. Typically relentless progressive disease leading to death
   10. If Gad must be used in patients with renal failure, dose should be substantially limited
   11. Unclear if dialysis following Gad use is of any benefit (syndrome is very rare)
   12. Reduce Gad use in any patient with glomerular filtration rate <30cc/min
8. Magnetic Resonance Angiography (MRA)
   1. Non-invasive visualization of cerebral and other vessels
   2. Gad at high dose is injected and MRI scan taken with 1-2 minutes
   3. Particularly useful in patients who will not tolerate iodine-based contrast agents
   4. Preferred initial test for ruling out many arterial diseases
   5. MRA is more sensitive and specific for 50% stenoses or total occlusion than either CT angiography or ultrasonography for lower limb peripheral artery disease [23]
   6. Reasonable for diagnosis of renal artery stenosis but sensitivity only ~60% [14]
9. MRI cannot be used in persons with:
   1. Ferromagnetic aneurysm clips
   2. Foreign objects in the eye
   3. Pacemakers
   4. Metal heart valves of certain types
   5. Other metal prostheses
10. Advantages of MRI
    1. Absence of ionizing radiation
    2. Highly sensitive to blood flow
    3. Images in any plane can be produced
    4. Detects iron in tissue
    5. Highly sensitive to edema
    6. Excellent visualization of the spinal cord
    7. Absence of beam hardening artifacts
11. Disadvantages of MRI
    1. Conventional MRI had long study times; ultrafast MRI speeds equal to CT
    2. About twice as expensive as CT
    3. Less sensitive than CT for calcifications
    4. Less sensitive that CT for acute hemorrhages
    5. Poor resolution of bony structure
12. Specialized MRI Methods
    1. Ultrafast MRI
    2. Echoplanar MRI - permits ultrafast images through improved gradient design
    3. Fluid-attenuated inversion recovery - low CSF signal, high signal for cerebral parenchymal lesions
    4. Diffusion-weighted imaging - detects cytotoxic edema, early ischemia
    5. MRI guided cardiac catheterization is feasible [10]
    6. Whole body MRI can be used for tumor staging, but is not as accurate as PET/CT [11]
13. MRI can be used for breast imaging rather than mammography [15]
    1. Sensitivity is superior to mammography (88%)
    2. Specificity ~68%
    3. Characteristics independent of breast density, tumor type, menopausal status
    4. Does not obviate need for breast biopsy
14. MRI in General Asymptomatic Population [22]
    1. Asympatomic brain infarcts present in 7.2%
    2. Cerebral aneurysms 1.8%
    3. Benign primary tumors 1.6%, mainly meningiomas
    4. Natural course of these lesions is not known

E. Positron Emission Tomography (PET)

1. Positron-emitting radioisotope labelled compound interacts with electrons
   1. The particular radiolabelled biological agent (tracer) determines what is measured
   2. The labelled compound is injected intravenously or inhaled
2. This leads to anihilation of both particles
3. The anihilation is accompanied by release of gamma rays (two photons)
4. The photons are released 180° from each other and are detected by monitors
5. Typical Radioisotopes and Compounds
   1. F(18)-fluorodeoxyglucose (FDG) - measuring cerebral metabolic rates for glucose
   2. O(15)-water - determining cerebral blood flow
   3. Carbon-11 - used to label many biological compounds for study
6. Highly versatile for studying a large variety of cerebral metabolic processes
7. Detection of Pulmonary Nodules [7,8]
   1. Optimal sensitivity and specificity of PET±FDG ~91% for detecting malignant lesions
   2. In current practice, sensitivity ~97% and specificity for malignant lesions ~78%
   3. Detection of lesions 1-3cm versus >3cm was similar
   4. PET+FDG may be suitable for noninvasively ruling out malignant pulmonary lesions
   5. PET+FDG appears to reduce number of unnecessary diagnostic surgeries by ~20% [8]
8. PET in Oncology [8]
   1. PET is more accurate than CT for detecting mediastinal lung cancers [9]
   2. Whole body imaging for tumor staging is possible
   3. PET(FDG) combined with CT is more accurate than MRI for tumor staging [11]
   4. PET can be used early on for assessment of response to tumor
   5. Likely more accurate than CT or MRI for detecting tumor recurrence
9. Disadvantages
   1. PET scans cost about twice as much as MRI
   2. A cyclotron is required to produce the radioisotopes for PET scanning

F. Single Photon Emission Computed Tomography (SPECT)

1. Theory is similar to PET scanning
   1. Different radioisotopes are used which have single photon emissions
   2. Xenon-133
   3. Technetium-99m-hexamethyl-propylamine-oxime
2. Generally used for investigation of blood flow
3. Restricted resolution and quantitation
4. Limited versatility for studying processes other than blood flow

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