Our institutional review board approved this prospective study, and informed consent for MRI was obtained from all patients. From November 2005 to July 2006, 59 patients with clinically suspected IIP were seen in an outpatient clinic by an experienced chest physician (11 years of experience in the diagnosis and management of IIP). From these 59 patients, we excluded 26 patients who had typical clinical and high-resolution CT features of UIP. Thus we included 33 consecutively registered patients who fulfilled the clinical and radiologic criteria for a diagnosis of IIP [1, 2] and who were candidates for surgical lung biopsy and underwent thoracic high-resolution CT and 3-T MRI. No patient in this group had a contraindication to MRI. These patients had no history of previous diagnosis of diffuse interstitial lung disease, known connective tissue disease, or corticosteroid use.

Biopsy specimens were obtained from multiple lung foci by use of video-assisted thoracoscopic surgery. Biopsy sites were chosen in consideration of high-resolution CT findings (areas containing ground-glass opacity irrespective of the presence of reticulation on coronal images). After pathologic evaluation of the 33 patients, seven patients with other than UIP or nonspecific interstitial pneumonia were excluded from data analysis. Three of the seven patients had cryptogenic organizing pneumonia, two had respiratory bronchiolitis–interstitial lung disease, and one each had desquamative interstitial pneumonia and lymphoid interstitial pneumonia. Thus we included 26 patients (10 men, 16 women; mean age, 57 ± 9 [SD] years; range, 37–70 years; mean body weight, 60 ± 8 kg; range, 44–79 kg) with UIP (n = 10) or nonspecific interstitial pneumonia (n = 16) in whom the expected pathologic findings were fibrosis and inflammation. Nine men and one woman were smokers (mean, 22 pack-years; range, 9–38 pack-years).

All MRI studies were performed with a 3-T system (Achieva, Philips Medical Systems) equipped with a gradient system capable of ensuring a maximum gradient amplitude of 80 mT/m, a rise time of 0.2 milliseconds, and a slew rate of 200 T/m/s. A cardiac coil (SENSE, Philips Medical Systems) with a six-coil element was used for coronal imaging of the thorax. After acquisition of T2-weighted triple-inversion black blood turbo spin-echo (TSE) images of the thorax, dynamic MRI was performed with a T1-weighted 3D turbo field-echo sequence before and after IV injection of contrast medium.

A breath-hold T2-weighted triple-inversion black blood TSE sequence with cardiac gating was performed with the following parameters: TR/TE, 1,200/1,800 (two R-R intervals); TE_eff, 60 milliseconds; echo-train length, 21; field of view, 420 mm; acquisition matrix size, 256 reconstructed to 512; slice thickness, 3 mm; interslice gap, 10 mm; coronal orientation. A double-inversion blood-nulling preparation pulse was applied at the R-wave trigger to suppress blood signal with an inversion delay of 697.6 milliseconds. The preparation pulse was followed by a third inversion pulse to generate spectral presaturation by inversion recovery contrast enhancement for fat suppression. This fat suppression was based on selective excitation of the lipid-bound proton by application of a frequency-selective inversion pulse. One slice acquisition per breath-hold was continued for 15 slices to cover the whole lung from back to front. The imaging time per breath-hold was 12 seconds, giving rise to a total acquisition time of 3 minutes. A sensitivity-encoding factor of 2 with one signal averaged was applied in the phase-encoding direction to increase acquisition speed.

Dynamic enhancement study of the lung parenchyma was performed with a T1-weighted 3D multishot turbo field-echo sequence. The sequence was optimized with a turbo field-echo factor of 60, turbo field-echo shots of 62, and a radial turbo direction with the following acquisition parameters: 2.7/1.34; flip angle, 10°; number of signals averaged, 1; field of view, 420 mm; acquisition matrix size, 192. Fat suppression was achieved with a spectral presaturation attenuated by inversion recovery method with an inversion delay of 90 milliseconds. Before IV injection of contrast medium, a slab in the coronal orientation covering the whole thorax was obtained in the back-to-front direction in one breath-hold. The slab thickness was 175 mm, and the slab was divided into 70 partitions to produce 70 images with 2.5-mm in section thickness. The imaging time per breath-hold was 22 seconds. To increase acquisition speed, a sensitivity-encoding factor of 2 was applied in the phase-encoding direction. An additional four slabs of images were obtained 1, 3, 5, and 10 minutes after manual IV bolus injection of gadopentetate dimeglumine (0.2 mL/kg of Magnevist, Bayer HealthCare). The parameters were the same as those used for the initial unenhanced series. All MR image data were directly interfaced to our PACS system (Pathspeed or Centricity 2.0, GE Healthcare), which displayed all image data on four monitors (1,536 × 2,048 image matrices, 8-bit viewable gray-scale, 60-ft-lambert luminescence). Dynamic enhanced images were viewed on the monitors.

Two chest radiologists unaware of clinical and pathologic information assessed all images together and made decisions on findings by consensus. For comparative study with pathologic results, biopsy sites on MR images, where the signal intensity of MR images was analyzed, were chosen in consideration of the biopsy sites on coronal CT scans (areas containing ground-glass opacity irrespective of the presence of reticulation), where biopsy had been recommended. The signal intensity (high, similar, or low in comparison with chest wall muscle) of parenchymal lung lesions on T2-weighted triple-inversion black blood TSE images was evaluated for each biopsy site.

Dynamic images were evaluated qualitatively and quantitatively. For qualitative analysis, enhancement pattern was visually assessed prospectively and classified into three categories at review of dynamic images: pattern 1, early enhancement and washout with discernible enhancement of peak enhancement at 1 or 3 minutes in dynamic study; pattern 2, slight enhancement with no discernible enhancement at specific time point throughout dynamic phases; pattern 3, delayed persistent enhancement with discernible peak enhancement at 5 or 10 minutes in dynamic study.

For the quantitative assessment of dynamic enhanced MR images, the mean signal intensity of the lesions was measured on PACS monitors by one of the two chest radiologists. A circular region of interest with an area of 100 mm² was placed at two or three surgical biopsy sites in the peripheral portion of the lungs. The areas were chosen in consideration of the high-resolution CT findings before biopsy and contained ground-glass opacity irrespective of the presence of reticulation. Each observer recorded the mean signal intensity. The percentage signal intensity of parenchymal lesions at a given time point (t) was determined with the following formula: percentage signal intensity = ([SI_t–SI_t0]/SI_t0) × 100%, where SI is signal intensity. The following parameters were evaluated: Maximum peak enhancement was determined as the maximum percentage signal intensity throughout the time points. Time to peak was defined as t_max – t₀ in minutes. Slope of enhancement was calculated as maximum percentage signal intensity/(t_max – t₀). Extent of washout was defined as maximum percentage signal intensity minus percentage signal intensity at t₁₀.

An experienced lung pathologist evaluated all pathologic specimens. Pathologic diagnoses were made according to the classification suggested in the 2002 consensus statement of the American Thoracic Society and European Respiratory Society [1]. Pathologic findings were divided into two groups, inflammation predominant and fibrosis predominant, by integration of the following semiquantitative evaluation results. Although there was no standardized scoring system for quantification of fibrosis and inflammation in IIP, after discussion with our experienced lung pathologist, we developed this system by modifying an existing system [26]. Semiquantitative evaluation included three types of histologic features: interstitial mononuclear cell infiltration, intra alveolar macrophages and exudates, and established fibrosis. Interstitial mononuclear cell infiltration was graded on a 5-point scale: 0, scanty; 1, scattered mononuclear cells; 2, patchy clustered mononuclear cells; 3, mononuclear cells with germinal center; 4, diffuse mononuclear cell infiltra tion. Intraalveolar macrophages and exudates was graded on a 3-point scale: 0, absent; 1, focal (< 10%) intraalveolar macrophage and exudates; 2, multiple patchy (> 10%) intra alveolar macrophage and exudates. Established fibrosis was quantified as percentage of dense fibrosis in a diseased area of a biopsy specimen (Figs. 1 and 2). If on histopathologic specimens, the biopsy site had a score of 2 or greater for interstitial mononuclear cell infiltration or intraalveolar macrophages and exudates and less than 10% fibrosis for established fibrosis, the biopsy site was classified inflammation predominant.

The chi-square test was used to compare the differences in signal intensity on T2-weighted triple-inversion black blood TSE MR images for the active inflammation and fibrosis-predominant groups. The chi-square test also was used to compare the frequency of the early enhancement pattern (pattern 1) on dynamic MRI for the active inflammation- and fibrosis-predominant histopathologic groups. The McNemar test was used to calculate and compare the diagnostic efficacies of the qualitative criteria of the early enhancement pattern (pattern 1) on dynamic MRI and of high signal intensity on T2-weighted triple-inversion black blood TSE MR images for differentiating inflammation- from fibrosis-predominant sites.

The Student's t test or Mann-Whitney U test, depending on the results of a normality (Kolmogorov-Smirnov) test, was used to compare quantitative parameters from time–intensity curves on dy namic MRI and semiquantitative histo patho logic scores between the inflammation-predo minant and fibrosis-predominant groups. In semi quant itative histopathologic scoring, this stati stical comparison was done to support the face validity of the scoring system. Spearman's rank correlation coefficients were used to estimate the relations between the quantitative parameters from dynamic MRI and semi quantitative histo pathologic scores. For all statistical analyses, p < 0.05 was considered significant.

Nine (53%) of 17 biopsy sites with an inflammation-predominant lesion had high signal intensity on T2-weighted triple-inversion black blood TSE images (Figs. 3 and 4), whereas four (11%) of 37 biopsy sites with a fibrosis-predominant lesion had high signal intensity (p = 0.001). The frequencies of lesion sites with high signal intensity on T2-weighted triple-inversion black blood TSE images were significantly different for inflammation- and fibrosis-predominant sites.

Visual assessment of dynamic enhancement patterns showed that 14 (82%) of 17 inflammation-predominant lesion sites exhibited early enhancement (pattern 1) and that 34 (92%) of 37 fibrosis-predominant lesion sites exhibited slight enhancement (pattern 2, n = 19) or delayed persistent enhancement (pattern 3, n = 15) (Figs. 5A, 5B, 5C, 5D, 5E, 5F, 6A, 6B, 6C, 6D, 6E, 6F, 7A, 7B, 7C, 7D, 7E, and 7F). The frequency of the early enhancement pattern (pattern 1) was significantly higher in the inflammation-predominant group (p = < 0.001) (Table 1). The three lesion sites, which did not exhibit early enhancement on dynamic MRI but had the histologic finding of inflammation predominance, were two lesion sites of group 1 nonspecific interstitial pneumonia with a slight enhancement pattern and one lesion site of group 1 nonspecific interstitial pneumonia with a delayed enhancement pattern.

The sensitivity, specificity, and accuracy of diagnostic criteria of the early enhancement pattern (pattern 1) on dynamic MRI were higher than those of high-signal-intensity lesions on T2-weighted triple-inversion black blood TSE MR images for differentiating inflammation-predominant and fibrosis-predominant sites, but the differences were not statistically significant (Table 2).

The results of analysis of time–intensity curve parameters for dynamic MRI are summarized in Table 3. Inflammation-predominant lesion sites had higher percentage signal intensity at 1 minute (p = 0.033), shorter time to peak (p = 0.032), and faster slope of enhancement (p = 0.010) than fibrosis-predominant sites. The extent of delayed enhancement was positively higher in the fibrosis-predominant group, but the difference between the two groups was not statistically significant (p = 0.067).

The semiquantitative scores of the three histologic features for interstitial mononuclear cell infiltration, intraalveolar macrophages and exudates, and established fibrosis are summarized in Table 4. Scores for interstitial mononuclear cell infiltration and intraalveolar macrophages and exudates were significantly higher for active inflammation sites (p = 0.003 and p < 0.001, respectively). Established fibrosis scores were significantly higher for fibrosis sites (p < 0.001). Slope of enhancement had a positive correlation with the inflammatory histologic features for interstitial mononuclear cell infiltration (r = 0.314) and intraalveolar macrophages and exudates (r = 0.306). Established fibrosis had a negative correlation with slope of enhancement (r = –0.389) and a positive correlation with time to peak (r = 0.436) and delayed enhancement (r = 0.361) (Table 5).