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Gerhard Kohl (pages 470–476) Figures 2, 5, 6, 9 and 11

View larger version (91K): [in this window] [in a new window]   Figure 2. Clinical example to illustrate the performance of 64-slice CT with z-flying focal spot: CT angiography of the carotid arteries and the circle of Willis. Scan parameters: 120 kV, 150 eff. mA, 64 x 0.6–mm collimation, 0.375-s gantry rotation time, pitch 1.4, scan time 6 s for 350 mm. The arrow indicates a severe stenosis. (Courtesy of Drs. Michael Lell and Katharina Anders, University of Erlangen, Erlangen, Germany.)

View larger version (42K): [in this window] [in a new window]   Figure 5. Schematic drawings of a conventional X-ray tube (top) and a rotating envelope tube (bottom). The electrons emitted by the cathode are represented by green lines, the X-rays generated in the anode are depicted as purple arrows. In a conventional X-ray tube, the anode plate rotates in a vacuum housing. Heat is mainly dissipated by thermal radiation. In a rotating envelope tube, the anode plate constitutes an outer wall of the tube housing and is in direct contact with the cooling oil. Heat is effectively dissipated by thermal conduction, and the cooling rate is significantly increased. Rotating envelope tubes have no moving parts and no bearings in the vacuum.

View larger version (73K): [in this window] [in a new window]   Figure 6. Picture of the STRATON tube (Siemens, Forchheim, Germany) as an example of a rotating envelope tube. The tube design is very compact; the anode diameter is only 12 cm.

View larger version (157K): [in this window] [in a new window]   Figure 9. Detector module of the SOMATOM Sensation 64 (Siemens). Each module consists of 40 x 16 detector pixels with the corresponding electronics. The antiscatter collimators are diagonally cut to open the view on the detector ceramics (yellow).

View larger version (54K): [in this window] [in a new window]   Figure 11. Peripheral CT angiography obtained on a 16-slice CT-system at 100-kV X-ray tube voltage. Compared with a standard scan at 120 kV, 30% less dose is necessary for equivalent signal-to-noise ratio. (Courtesy of Klinikum Grosshadern, Munich, Germany.)

Erik L. Ritman (pages 477–480) Figure 3

View larger version (100K): [in this window] [in a new window]   Figure 3. Micro-CT image of an isolated biopsy of a pig's lung after injection of Microfil into its aorta. Left panel: CT image through the specimen. The voxel size was 20 µm. The white spots are a cross section of opacified bronchial arteries, and the black "holes" are air-filled lumens of bronchi. Right panel: Volume-rendered display of the bronchi (yellow) and bronchial arterioles (red).

Laurence W. Hedlund and G. Allan Johnson (pages 481–483) Figures 1, 2, 4, 5 and 6

View larger version (124K): [in this window] [in a new window]   Figure 1. (A–C) Axial views of a 19-g mouse showing major thoracic structures from most cranial level (A) to the most caudal level (C). Images on the right show labels for the same images on the left. Right lung: AC LR = accessory lobe; Ao V = aortic valve; Asc Ao = ascending aorta; AZ V = azygous vein; Caud VC = caudal vena cava; Cr LR = cranial lobe right; Dsc Ao = descending aorta; Eso = esophagus; L Cran VC = left cranial vena cava; LA = left atrium; LL = left lung; LLR = lower/caudal lobe; LV = left ventricle; MLR = middle lobe; PA = pulmonary artery; PV = pulmonary vein; R Cran VC = right cranial vena cava; RA = right atrium; RV = right ventricle. Separation in mm between levels: A–B = 1.13; B–C = 3.4; total (A–C) = 4.6 mm, slice thickness = 0.063 mm.

View larger version (17K): [in this window] [in a new window]   Figure 2. (A–E) Schematic waveforms illustrate how magnetic resonance imaging (MRI) data acquisition (E) is triggered (D) in synchrony with the cardiac cycle (B) and breathing cycle (A) during expiration (EXP) or inspiration (INS). Left side shows imaging during EXP. Right side shows imaging during peak INS.

View larger version (95K): [in this window] [in a new window]   Figure 4. Anesthetized 250-g rat positioned in a Plexiglas cradle (6.3-cm diameter) supported by white Delrin rings (15-cm diameter) for imaging in a 2-T magnet with a 15-cm diameter bore. The transmit/receive radiofrequency imaging coil is seen covering the chest and abdomen positioned between the white support rings. The coil operates at two frequencies for hydrogen and helium imaging. The animal's endotracheal tube is connected directly to an MR-compatible breathing valve, which is connected to power and breathing air supply hoses. The animal is instrumented with ECG electrodes attached to the paws and rectal temperature probe.

View larger version (126K): [in this window] [in a new window]   Figure 5. Coronal slabs (five 2-mm slices combined, 100 µm in-plane) from an anesthetized live rat being respirated with a combination of hyperpolarized 3He and air (left) or air only (center). Both images are shown superimposed on the right. For details, see Johnson and colleagues (23).

View larger version (69K): [in this window] [in a new window]   Figure 6. Coronal images of a rat 6 mo after right lung irradiation. (a) 1H, (b) 3He, (c) hematoxylin and eosin (H&E), and (d) Masson's trichrome show significant damage to the right lung. Damage seen in the in vivo MRI corresponds to areas of severe fibrosis found on H&E and Masson's sections. Bar, 5 mm. Reprinted with permission from Reference 24.

Juerg Tschirren, Eric A. Hoffman, Geoffrey McLennan, and Milan Sonka (pages 484–487) Figures 2, 3, 4 and 5

View larger version (47K): [in this window] [in a new window]   Figure 2. Comparison of typical segmentation results obtained by the conventional region-growing method (a) and the new method (b) in a low-dose scan.

View larger version (37K): [in this window] [in a new window]   Figure 3. Quantitative analysis. Two-dimensional slices are resampled perpendicular to the centerline; the inner border is detected; and cross-sectional area, minor diameter, and major diameter are computed.

View larger version (149K): [in this window] [in a new window]   Figure 4. Border position can be modified by adjusting the value of the first and second derivative weighting factor (described in text). Note that the border positioning and, consequently, the measured airway size depend on the value of . The correct value of the parameter is obtained by training in comparison with an independent standard. Because the independent standard is typically not available for in vivo images, training is performed in computed tomography (CT)–scanned phantoms.

View larger version (136K): [in this window] [in a new window]   Figure 5. Analysis of the airway tree path between the trachea and a sixth-generation airway distal to segment LB8. Note the anatomic labeling of the individual airway tree segments. This labeling is obtained automatically. (a) Straightened axial image of a normal airway. (b) Straightened axial image of a cystic fibrosis airway. (c) Airway tree path analyzed in a marked on a three-dimensional tree rendering of the analyzed normal tree. (d) Normalized chart of airway diameter as a function of location, demonstrating the exceedingly increased diameters of distal airway segments in cystic fibrosis. LB8 = left bronchus segment 8; LLB6 = left lower bronchus segment 6; LMB = left main bronchus; TriLLB = left lower bronchus trifurcation.

J. Scott Ferguson and Geoffrey McLennan (pages 488–491) Figures 1, 2, 3, 4

View larger version (30K): [in this window] [in a new window]   Figure 1. Left panel: the relationships between the trachea, a paratracheal abscess, and the carotid artery. Center panel: a patient with severe subglottic stenosis from Wegener's granulomatosis, with the manubrium sterni in correct position, showing there is room for a tracheostomy. Right panel: lateral view of a large thyroid goiter, displacing and compressing the trachea, with no room for a tracheostomy above the manubrium sterni.

View larger version (59K): [in this window] [in a new window]   Figure 2. Example of transbronchial lymph node biopsy using multidetector computed tomographic (CT) information. On the left panel is the computer-rendered virtual bronchoscopy view, with the lymph node region of interest shown through the wall as a dark blue-black. On the right panel, the lymph node region of interest is transposed to the real bronchoscopic view. The point to place the transbronchial needle is now easily identified.

View larger version (45K): [in this window] [in a new window]   Figure 3. Screen shot of a pulmonary pathfinding program using virtual bronchoscopy advanced applications. On the left panel is shown the extracted bronchial tree, with the balloon shapes quantitatively showing pulmonary emphysema. There is a pathfinding tool, which connects the emphysema regions through their subtending airways to the trachea, to allow for both sampling to be performed bronchoscopically and planning for bronchoscopic lung volume–reduction surgery. The right panel is the virtual bronchoscopy fly-through at the level of the small white square shown through the trachea at this time.

View larger version (60K): [in this window] [in a new window]   Figure 4. All of these panels are representations of serious pathology with an obstructing tumor in the right main bronchus. The two upper panels represent a fluorescein bronchoscopic angiogram showing early mucosal fluorescence. The two lower panels show the color bronchoscopy pictures on the right with the fluorescence angiogram results now fused into this dataset shown on the left. The panel on the far right shows the airway tree with CT-derived virtual bronchoscopy, with the real bronchoscopic images in the left panels now fused into the three-dimensional CT dataset. This image is now viewable in three-dimensional space with any angle of view for assessment of structure, and with the fluorescein angiogram information, also assessment of function (a true four-dimensional virtual bronchoscopic image).

Eric A. Hoffman and Deokiee Chon (pages 492–498) Figures 2 and 3

View larger version (82K): [in this window] [in a new window]   Figure 2. Color maps of regional pulmonary blood flow in nonsmoking and smoking subjects. Note the increased heterogeneity of flow in the smoker, presumably indicating the results of inflammatory processes. The color scales under each image range from 0 to 15 ml/min/g.

View larger version (73K): [in this window] [in a new window]   Figure 3. Color maps of regional specific ventilation (left), regional perfusion (middle), and regional / (right) in a prone sheep. Because of the simultaneously derived anatomic detail via CT, we are able to express ventilation and perfusion through normalization to air, tissue, or blood content of the region. To achieve a measure of regional specific ventilation, one would normalize the measures of ventilation to regional air content. However, here we simply express ventilation and perfusion as a function of voxel volume because / provides self-normalization.

Brett A. Simon, Gary E. Christensen, Daniel A. Low, and Joseph M. Reinhardt (pages 517–521) Figures 1, 2 and 3

View larger version (63K): [in this window] [in a new window]   Figure 1. Example of the image registration process, in which a human lung computed tomography (CT) image at functional residual capacity (FRC) is mapped to total lung capacity (TLC). The mathematical transform defined is applied to the FRC image, and the original TLC slice is seen to closely resemble the corresponding "warped" FRC slice.

View larger version (78K): [in this window] [in a new window]   Figure 2. Color-coded log-Jacobian (quantitative regional expansion or contraction) images superimposed on the target CT volume for 15 images obtained from a human subject during three spontaneous breaths. I: log-Jacobian superimposed on the CT slice for each of the 14 image registrations. The subscripts for each panel correspond to the points in the respiratory cycle (II) at which the image pairs were obtained. Magenta corresponds to a contraction, red corresponds to an expansion, and green corresponds to no change. III: Correlation between the average log-Jacobian and the volume changes measured by spirometry.

View larger version (100K): [in this window] [in a new window]   Figure 3. Image-based computational model of sheep lung mechanics (66). Finite element meshes of a sheep lung at distending pressures of 0, 20, and 25 cm H2O demonstrate simulated deformation from 25 cm H2O (wireframe mesh). Also shown are the CT-based airway tree and generated volume-filling small airways (at 25 cm H2O; bottom right) embedded within the finite element mesh. Figure reprinted by permission from M. Tawhai (University of Auckland, Auckland, New Zealand). Paw = airway pressure.

Guido Musch and Jose G. Venegas (pages 522–527) Figures 2, 3 and 4

View larger version (64K): [in this window] [in a new window]   Figure 2. PET images obtained from an animal after saline lung lavage, in supine and prone positions. Four slices of lung are shown in each vertical panel (top to bottom, cranial to caudal). For each body position, the images in the first panel correspond to the peak of the infused 13N2 kinetics (5 s < t < 10 s) and represent the regional distribution of perfusion (peak apnea image). Note the preferential distribution of perfusion to dorsal regions in both positions, and the more uniform perfusion when prone. The images in the second panel correspond to the plateau of the infused 13N2 kinetics (40 s < t < 60 s) and show the regional distribution of perfusion in units that are perfused and aerated (end apnea image). Regions of shunt, which do not retain 13N2 during apnea, can be visualized as regions in which tracer activity is present in the peak apnea images but absent in the end apnea images. Note the large amount of shunt in dorsal regions, particularly of caudal slices, in the supine position, which is annihilated by turning prone. This is consistent with the regional distribution of gas fraction, measured after equilibration of inhaled 13N2 (third panel), which shows restored aeration to dorsal regions and more uniform aeration in the prone position. Reprinted by permission from Reference 29.

View larger version (47K): [in this window] [in a new window]   Figure 3. PET images of intrapulmonary 13N2 concentration after a bolus intravenous infusion of 13N2–saline in a supine asthmatic subject at baseline (top) and during methacholine-induced bronchoconstriction (bottom). In each of the four panels, slices from three regions of lung are shown (top to bottom: cranial, middle, and caudal). In each slice, the right lung is on the right side and the left lung on the left. The color-coded activity scale refers to the mean-normalized activity of the images within each panel, to show the relative distribution of 13N2 in the images corresponding to each condition. The panels on the left show the intrapulmonary distribution of 13N2 during apnea and represent the regional distribution of perfusion. The panels on the right show residual 13N2 at the end of a 3-min tracer washout by spontaneous breathing and represent the regional distribution of tracer retaining (i.e., hypoventilated) regions. Note that: (1) Perfusion is distributed heterogeneously in this subject with asthma, both when asymptomatic at baseline and during methacholine-induced bronchoconstriction (apnea images). (2) End washout images show large regions of tracer retention, particularly during bronchoconstriction. (3) The location of tracer retaining regions tends to be inverted after methacholine inhalation compared with baseline: regions that are hypoventilated at baseline become relatively more ventilated after methacholine inhalation (e.g., the dorsal cranial region of the left lung), whereas regions that are well ventilated at baseline tend to become relatively hypoventilated (e.g., the middle region of the right lung). This suggests that regions that are constricted at baseline are protected from bronchoconstriction induced by inhaled methacholine. (4) During bronchoconstriction, regions that become hypoventilated tend to be relatively less perfused than regions with higher ventilation (e.g., compare the ventral caudal region of the right lung with the dorsal caudal region of the same lung). This observation is consistent with the effect of hypoxic pulmonary vasoconstriction promoting redistribution of perfusion to match heterogeneous ventilation during bronchoconstriction.

View larger version (62K): [in this window] [in a new window]   Figure 4. Volumetric rendering of the intrapulmonary distribution of 13N2-retaining regions in a subject with asthma during methacholine-induced bronchoconstriction (foreground) and two-dimensional display of the distribution of ventilation predicted by a theoretic model of the constricting airway tree (background). In the volumetric rendering, the blue surface delineates the lung boundaries of a 10-cm long cross-section of thorax and the red surface delineates a hypoventilated region that retained 13N2. For reference, the central airways were imaged with PET by inhalation of an aerosol containing 13N-ammonia (13NH3) and are delineated in yellow. Ventilation defects predicted by the theoretic model (background) are represented by terminal units in black and brown at the end of a 12-generation Mandelbrot tree.

Edwin J. R. van Beek and Jim M. Wild (pages 528–532) Figure 2

View larger version (95K): [in this window] [in a new window]   Figure 2. Ventilation distribution image, apparent diffusion coefficient (ADC) map, and histogram of ADC values in (A) a normal volunteer, (B) a healthy smoker, and (C) a patient with emphysema. COPD = chronic obstructive pulmonary disease. Reprinted with permission from Reference 32.

Arion F. Chatziioannou (pages 533–536) Figures 2 and 3

View larger version (44K): [in this window] [in a new window]   Figure 2. (A) Illustration of the principle of PET. (B) Illustration of the principle of pinhole single-photon emission computed tomography.

View larger version (49K): [in this window] [in a new window]   Figure 3. 9-(4-18F-fluoro-3[hydroxymethyl]butylguanine (FHBG) scan of HSV-tk–transfected liver. Coronal projections from a dynamic sequence of tomographic images from a mouse as it is injected with a bolus of a liver-specific tracer. The graph illustrates the concentration of the compound on different organs as a function of time. The panel on the right has a projection of fused datasets, anatomic from X-ray micro–computed tomography and functional from small-animal PET. HSV-tk = herpes simplex virus thymidine kinase gene.

Ruxana T. Sadikot and Timothy S. Blackwell (pages 537–540) Figures 1 and 2

View larger version (88K): [in this window] [in a new window]   Figure 1. Bioluminescent imaging of HLL mice at 0–48 h after a single intraperitoneal (IP) injection of LPS (2 µg/g) or LPS delivered to the peritoneal cavity by osmotic pump (LPS pump). A representative HLL mouse imaged repeatedly after a single IP injection of LPS (upper panel) or after implantation of an LPS pump (lower panel) is shown. For imaging, luciferin (3 mg) was given by IP injection, and photon emission was detected 30 min later. The scale for the pseudocolor images, indicative of relative pixel intensity, is shown at the left.

View larger version (114K): [in this window] [in a new window]   Figure 2. Bioluminescent images of HLL mice are shown at baseline (A) or 24 h after intratracheal injection of P. aeruginosa at 105 (B), 106 (C), or 107 (D) colony-forming units. The circle represents the region of interest used for quantitation of photon emission. Reprinted by permission from Reference 37.

Delphine L. Chen and Farrokh Dehdashti (pages 541–544) Figure 1

View larger version (124K): [in this window] [in a new window]   Figure 1. Coronal (top row) and transaxial (bottom row) FDG-PET/CT images of a patient with NSCLC. CT images (left), PET images (right), and fused PET-CT images (middle) are shown. There is increased uptake within the primary lung cancer in the right lower lobe (straight arrow, bottom middle image). Metastatic involvement of an enlarged subcarinal lymph node (curved arrow) and a small right hilar node (block arrow, top middle image) are evident.

Hazel A. Jones (pages 545–548) Figures 1, 3 and 4

View larger version (93K): [in this window] [in a new window]   Figure 1. White blood cell scans of neutrophil migration (left) with PET images (right) in a patient 3 d after onset of symptoms of acute lobar pneumonia (top) and a patient with chronic bronchiectasis (bottom). White cell scans are clearly negative in pneumonia and positive in bronchiectasis. PET scans show transmission image, initial distribution after intravenous injection of 18FDG, and localization to affected lobe in the patient with pneumonia at 1 h. There is no apparent increase in 18FDG uptake in the patient with bronchiectasis. Adapted by permission from Reference 12.

View larger version (112K): [in this window] [in a new window]   Figure 3. PET emission images of rabbit thorax following intravenous [11C]-R-PK11195 3 d (top) and 6 d (bottom) after challenge with 50 mg of 5-µm particles of microcrystalline silica (left) or amorphous (nonfibrogenic) silica (right) into the right upper lobe of rabbit lung. Localization of radioactivity is to the challenged region (red arrows) at 3 d. By 6 d there is a second signal (white arrow) indicating clearance of particle-bearing macrophages through the lymphatics. Adapted by permission from Reference 21.

View larger version (96K): [in this window] [in a new window]   Figure 4. Left-hand panel: PET images of rabbit 6 wk after instillation of microcrystalline silica into the right upper lobe. The top image shows the distribution of tissue density; the green-black low-density lungs are clearly delineated. Regions of interest are drawn around the lung regions (white). These regions of interest are shown transferred onto the emission images below. Distribution of [18F]-fluoroproline at 90 min after injection shows radioactivity localized to the challenged lung. Right-hand panel: Autoradiography of [3H]-proline distribution carried out 13 wk after instillation of microcrystalline silica. The control lung (A) shows normal architecture and autoradiographic grains are random and represent distribution of [3H]-proline in biofluid with no localized uptake. The challenged lung (B) shows disruption of the architecture and massive interstitial thickening. Autoradiographic grains are associated with the cellular component of the lesion (arrows), principally fibroblasts (probably myofibroblasts). The acellular area in the center of the lesion (starred) shows no increase in radiolabel. Refractile silica particles are indicated by drum-sticks. Adapted by permission from Reference 33.

Sekhar Dharmarajan and Daniel P. Schuster (pages 549–552) Figures 1, 2, 3, 4, 5 and 6

View larger version (55K): [in this window] [in a new window]   Figure 1. Modern portfolio of imaging techniques. Top left: Cross-sectional image by micro–X-ray computed tomography of the mouse thorax. Top right: Short-axis echocardiographic views of two different rats. The one on the left shows normal right ventricular (RV) and left ventricular (LV) dimensions, whereas the one of the right shows marked RV dilation due to experimentally induced pulmonary hypertension. Bottom: Multimodality overlay image combining X-ray computed tomography with micro–positron emission tomography (micro-PET) imaging of a rat 5 d after administration of an adenovector carrying a PET reporter gene capable of trapping a radiolabeled substrate in tissues expressing the gene product to a donor rat, and 4 d after left lung transplantation of the transfected lung.

View larger version (112K): [in this window] [in a new window]   Figure 2. Platforms for gene expression imaging of the lungs in small animals. (A) Cradle for immobilizing anesthetized mice. Fiducial markers for coregistration of images from different modalities are embedded into the cradle. (B) Apparatus used to provide continuous gas anesthesia during imaging. (C) A MicroCAT II scanner (ImTek/CTI Molecular Imaging, Knoxville, TN). (D) A microPET R4 scanner (CTI Concorde Microsystems, Knoxville, TN). The two scanners are in the same room and mice are moved from one device to the other while remaining anesthetized and immobilized in the cradle.

View larger version (35K): [in this window] [in a new window]   Figure 3. Schematic representation of a single tomographic cross-section through the chest at the midventricular level, surrounded by one ring of radiation detectors. After a positron–electron interaction (point A), high-energy photons are given off; photons arriving at the darkened detectors within an allowable "coincidence window" are recorded and used in later image reconstruction. As multiple detector pairs are included, the activity emitted from the radiation source at the point of intersection is located with increasing accuracy.

View larger version (48K): [in this window] [in a new window]   Figure 4. Principles underlying reporter transgene expression imaging by PET. A vector (in this case, an adenovirus) is used to introduce the PET reporter gene (in this case, the herpes simplex virus-1 [HSV-1] thymidine kinase gene; HSV1-tk) into a target cell, such as the lung airway epithelium. The gene is transcribed and translated into the thymidine kinase protein (HSV1-TK). The viral TK enzyme has a relaxed substrate specificity compared with mammalian TK, allowing it to phosphorylate (and trap) the radiolabeled reporter probe 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG).

View larger version (43K): [in this window] [in a new window]   Figure 5. Major components of a gene expression imaging study. (A) A vector is chosen for reporter gene delivery. In this case, the vector is a human type 5 replication-deficient (E1a/E3-deleted) fusion gene of a mutant HSV1-tk gene and enhanced green fluorescent protein gene (egfp) driven by the cytomegalovirus (CMV) promoter. Tissues that express the protein product of tk can phosphorylate and trap radiolabeled substrates. Accumulation of the radiolabel in tissues generates an imaging signal detectable by a PET scanner. (B) An imaging protocol is devised. In this case, multiple images are obtained dynamically over an 80-min period after administration of a substrate for the viral thymidine kinase [18F]FHBG. These images can be used to generate time–activity curves for kinetic modeling of tracer uptake. Alternatively, in some cases, a single scan, typically performed after clearance of the tracer from the blood is near maximal, can be used. (C) Single transverse images obtained approximately 80 min after [18F]FHBG administration to rats at various times after administration of an adenovector carrying the tk reporter gene. Gene expression is detected within 6 h of adenovector administration, is maximal at 4 d, and decreases thereafter. ID = injected dose.

View larger version (75K): [in this window] [in a new window]   Figure 6. Serial in vivo cross-sectional images through rat lung of [18F]FHBG distribution after transfection with the PET reporter gene mHSV1-tk, using a surfactant vehicle (A) and a saline vehicle (B). The pixels within each region of interest drawn on each slice are colored pale blue. Pixels with radioactivity values greater than 0.3% of the injected dose of [18F]FHBG per milliliter (shown in the study to be the upper limit of expression when the adenovector was delivered in saline) are recolored red. The images show that the increase in gene transfer with adenovector delivered in surfactant occurs throughout the lungs. Reprinted by permission from Reference 26.

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