Our laboratory has been involved in tomosynthesis research for over 20 years. In that time we have developed our own tomosynthesis deblurring algorithm, Matrix Inversion Tomosynthesis (MITS), and have investigated tomosynthesis applied to the detection of pulmonary nodules. (See additional page for description of the technical elements of tomosynthesis optimization). This research has been supported by seven years of grant funding from NIH (R01 CA080490) aimed at optimizing the technique and evaluating it in a clinical trial. Our initial results have demonstrated strong improvement in detection of lung nodules with tomosynthesis compared with conventional PA chest radiography.  A commercial tomosynthesis device is now on the market (GE Healthcare) as a result of collaboration with our laboratory.

Clinical trial results
Our NIH-funded clinical trial has collected tomosynthesis and conventional chest radiographs from 97 human subjects. After a pilot study with 20 subjects, we performed interim analysis of the next twenty-one subjects to evaluate the sensitivity of detection of small lung nodules. Patients undergoing CT to follow up lung nodules were consented and enrolled to receive an additional digital PA chest radiograph and digital tomosynthesis exam. Tomosynthesis was performed with a commercial CsI/a-Si flat-panel detector and a custom-built tube mover. Seventy-one images were acquired in 11 sec, reconstructed with the MITS algorithm at 5-mm plane spacing, and then averaged (7 plane running average) to reduce noise and low-contrast artifacts. Total exposure for tomosynthesis imaging was equivalent to that of 11 digital PA radiographs (comparable to a typical screen-film lateral radiograph or two digital lateral radiographs). CT scans (1.25-mm section thickness) were reviewed to confirm presence and location of nodules.

Three chest radiologists independently reviewed tomosynthesis images and PA chest radiographs to confirm visualization of nodules identified by CT. Nodules were scored as: definitely visible, uncertain, or not visible. 175 nodules (diameter range 3.5-25.5 mm) were seen by CT and grouped according to size: < 5-mm, 5-10-mm, and >10-mm. When considering as true positives only nodules that were scored definitely visible, sensitivities for all nodules by tomosynthesis and PA radiography were 70% (±5%) and 22% (±4%), respectively (p<0.0001). Digital tomosynthesis showed significantly improved sensitivity of detection of known small lung nodules in all three size groups when compared to PA chest radiography (Table 1).

Figure 1 shows an example of the improved visibility of pulmonary nodules with tomosynthesis. Figure 2 shows that tomosynthesis can also be used to rule out false positives such as rib osteophytes.

Figure 1. Images of nodules in one of the human subjects. (a: top left) Coned view of digital PA radiograph shows one clearly visible right lung nodule (arrow). (b: top right) Tomosynthesis image shows the same nodule (vertical arrow) as seen on the PA radiograph in (a). A second nodule (horizontal arrow) is also visible that was not seen in the PA radiograph in (a). (c: bottom left) Tomosynthesis image at a more posterior level shows an additional left lung nodule (arrow) not seen in the PA radiograph in (a). (d: bottom right) CT image (lung window) confirms left lower lobe nodule seen in (c). (From Medical Physics 35:2554-2557, 2008)

Figure 2. Images of a suspicious lesion. (a) A nodule-like opacity was noted in the PA radiograph (left). (b) The tomosynthesis images revealed it to be a rib osteophyte and ruled out a pulmonary nodule (right). This finding demonstrates that tomosynthesis may not only improve sensitivity but may also potentially improve specificity by ruling out nodule mimics.

Ongoing work

This interim report was the first published demonstration of improved sensitivity with chest tomosynthesis using a flat-panel tomosynthesis system. While these results were very encouraging and strongly suggest that tomosynthesis will improve clinical detection of pulmonary nodules, these results need to be confirmed in the larger cohort of subjects. An observer study is underway to evaluate both sensitivity and specificity in the full set of 77 human subject cases. We also will evaluate the sensitivity and specificity of tomosynthesis compared with dual-energy in this ongoing observer study (see web page on dual-energy radiography).

Representative publications

• J. T. Dobbins, III and D. J. Godfrey, "Digital x-ray tomosynthesis: current state of the art and clinical potential," Phys. Med. Biol. 48, R65-R106 (2003).
• McAdams HP, Samei E, Dobbins JT III, Tourassi GT, Ravin CE: Recent advances in chest radiography. Radiology 241:663-683, 2006.
• Dobbins JT III, McAdams HP, Godfrey DJ, Li CM: Digital tomosynthesis of the chest. J Thoracic Imag 23(2):86-92, 2008.
• Dobbins JT III, McAdams HP, Song J-W, Li CM, Godfrey DJ, DeLong DM, Paik S-H, Martinez-Jimenez S: Digital tomosynthesis of the chest for lung nodule detection: interim sensitivity results from an ongoing NIH-sponsored trial. Medical Physics 35(6):2554-2557, 2008.
• Dobbins JT III: Tomosynthesis imaging: at a translational crossroads. Medical Physics36(6):1956-1967, 2009.
• Dobbins JT III, McAdams HP: Chest tomosynthesis: technical principles and clinical update. European J Radiology (in press), 2009.

Acknowledgments
Grant support for this project was provided by the National Institutes of Health (R01 CA080490) and GE Healthcare. Duke University and GE Healthcare jointly hold a patent on tube movement strategy in tomosynthesis.