DOI:10.2214/AJR.07.2833
AJR 2008; 190:878-885
© American Roentgen Ray Society
3-T MRI for Differentiating Inflammation- and Fibrosis-Predominant Lesions of Usual and Nonspecific Interstitial Pneumonia: Comparison Study with Pathologic Correlation
Chin A Yi1,
Kyung Soo Lee1,
Joungho Han2,
Man Pyo Chung3,
Myung Jin Chung1 and
Kyung Min Shin1
1 Department of Radiology and Center for Imaging Science, Samsung Medical
Center, Sungkyunkwan University School of Medicine, 50, Ilwon-dong,
Gangnam-gu, Seoul 135-710, Korea.
2 Department of Pathology, Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul, Korea.
3 Division of Pulmonary and Critical Care Medicine, Department of Medicine,
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea.
Received July 7, 2007;
accepted after revision October 29, 2007.
Presented at the 2006 scientific assembly of the Radiological Society of
North America, Chicago, IL (SSQ05-03).
Supported by Samsung Medical Center Clinical Research Development Program
grant CRDP CRS106-40-2.
Address correspondence to K. S. Lee
(kyungs.lee{at}samsung.com).
Abstract
OBJECTIVE. The purpose of our study was to evaluate the utility of
3-T MRI of the lung for differentiating inflammation- and fibrosis-predominant
lesions in the usual and nonspecific types of interstitial pneumonia.
SUBJECTS AND METHODS. The subjects were 26 patients (10 men, 16
women; mean age, 57 ± 9 [SD] years; 16 with nonspecific interstitial
pneumonia; 10 with usual interstitial pneumonia) who underwent 3-T MRI of the
lung and surgical biopsy. A total of 54 biopsy sites were classified
histopathologically into two groups: inflammation predominant and fibrosis
predominant. After a T2-weighted triple-inversion black blood turbo spin-echo
(TSE) sequence, dynamic MRI was performed with a T1-weighted 3D turbo
field-echo sequence (coronal images with 2.5-mm slice thickness) before and 1,
3, 5, and 10 minutes after IV contrast injection. The chi-square test was used
to compare differences in signal intensity on T2-weighted triple-inversion
black blood TSE MR images and visually assessed enhancement patterns at
dynamic MRI for the inflammation- and fibrosis-predominant sites.
RESULTS. Inflammation-predominant specimens were obtained from 31%
(17 of 54) of the biopsy sites. Inflammation-predominant biopsy sites had an
early enhancement pattern (82%, 14 of 17 sites, p < 0.001) on
dynamic studies and high signal intensity (53%, nine of 17 sites, p =
0.001) on T2-weighted triple-inversion black blood TSE images.
CONCLUSION. Multiphase dynamic enhancement studies with a turbo
field-echo sequence and T2-weighted triple-inversion black blood TSE images on
3-T MRI appear to be useful for differentiating inflammation- and
fibrosis-predominant lesions.
Keywords: idiopathic interstitial pneumonia • MRI • 3 T
Introduction
Idiopathic interstitial pneumonia (IIP) is a heterogeneous group of
nonneoplastic disorders resulting from lung parenchymal damage by varying
combinations of inflammation and fibrosis. An international standard was
established in 2002 in a consensus statement by the American Thoracic Society
and European Respiratory Society
[1,
2]. In the statement, the
primary role of high-resolution CT was confined to differentiating patients
with typical findings of idiopathic pulmonary fibrosis (histologically usual
interstitial pneumonia [UIP]) from those with the less-specific findings
associated with other types of IIP
[3,
4]. Surgical lung biopsy is
advised for patients with suspected IIP who do not have classic
high-resolution CT features of idiopathic pulmonary fibrosis in the absence of
a contraindication [5].
Histopathologic distinction between inflammation- and fibrosis-predominant
lesions is considered a major determinant of clinical characterization and
prognosis of IIP [6,
7]. On high-resolution CT,
disease patterns sometimes overlap between sites of active inflammation and
fibrotic lesions; thus similar patterns of diseased segments on CT can have
different responses to treatment
[8].
An inherent feature of MRI is high tissue contrast; thus MRI is generally
expected to be useful for differentiation of active inflammatory and fibrotic
lung lesions. In an initial report
[9], the presence of
high-signal-intensity lesions was considered a useful predictor of treatment
response and clinical outcome. Subsequent studies focused on the enhancement
pattern of IIP lesions on MRI. Lesions with active alveolitis had prominent
enhancement, whereas fibrotic lesions did not
[10,
11]. Despite the advantages of
MRI for differentiating inflammation- and fibrosis-predominant lesions, the
merits of MRI over CT have been questioned in terms of utility in the
evaluation of parenchymal lung lesions because MRI has inferior anatomic
resolution and is compromised by inevitable artifacts due to motion and
susceptibility effects [12,
13].
Technical developments in MRI and refinement of pulse sequences have
improved the quality and speed of imaging
[14–19].
In addition, high-field-strength MRI has increased signal-to-noise ratios
during thoracic imaging [20].
High-field-strength MRI for lung imaging has been found to have sensitivity
comparable with that of CT in the detection of diffuse lung disease
[21]. These properties have
facilitated the use of MRI to evaluate the dynamic enhancement patterns of
lung lesions and to depict in detail the anatomic features of interstitial
lung disease
[22–25].
The purpose of our study was to evaluate the utility of 3-T lung MRI for
differentiating inflammation- and fibrosis-predominant lesions in UIP and
nonspecific interstitial pneumonia.
Subjects and Methods
Patient Enrollment
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).
Lung MRI at 3 T
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); TEeff, 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 x
2,048 image matrices, 8-bit viewable gray-scale, 60-ft-lambert luminescence).
Dynamic enhanced images were viewed on the monitors.
Image Analysis
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 =
([SIt–SIt0]/SIt0)
x 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
tmax – t0 in minutes. Slope of
enhancement was calculated as maximum percentage signal
intensity/(tmax – t0). Extent of
washout was defined as maximum percentage signal intensity minus percentage
signal intensity at t10.
Pathologic Analysis
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.
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Fig. 1 —48-year-old woman with nonspecific interstitial pneumonia
(group 1, cellular). Photograph of pathologic specimen at low magnification
shows predominant inflammation. Scores for individual histologic features were
interstitial mononuclear cell infiltration, 2; intraalveolar macrophages and
exudates, 2; established fibrosis, 10. (H and E, x100)
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Fig. 2 —47-year-old woman with nonspecific interstitial pneumonia
(group 3, fibrotic). Photograph of pathologic specimen at high magnification
shows advanced fibrosis. Scores for individual histologic features were
interstitial mononuclear cell infiltration, 1; intraalveolar macrophages and
exudates, 1; established fibrosis, 50. (H and E, x200)
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Statistical Analysis
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.
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Fig. 3 —59-year-old woman with active inflammatory idiopathic
interstitial pneumonia: nonspecific interstitial pneumonia (group 1, cellular)
with acute exacerbation. Coronal T2-weighted triple-inversion black blood
turbo spin-echo image shows bilateral high-signal-intensity lesions
(arrows) in lower lung zones. Histopathologic examination of biopsy
specimen obtained from right lower lobe disclosed active inflammatory
disease.
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Results
The 26 patients had the following final histopathologic diagnoses: UIP
(n = 10; 22 biopsy specimens; two inflammation- and 20
fibrosis-predominant lesions), group 1 nonspecific interstitial pneumonia
(n = 5; 11 biopsy specimens; 10 inflammation- and one
fibrosis-predominant lesions); group 2 nonspecific interstitial pneumonia
(n = 2; five biopsy specimens; two inflammation- and three
fibrosis-predominant lesions), and group 3 nonspecific interstitial pneumonia
(n = 9; 16 biopsy specimens; three inflammation- and 13
fibrosis-predominant lesions). After acquisition and analysis of
histopathologic specimens from multiple biopsy sites in these 26 patients, a
total of 54 lesion sites were designated inflammation predominant (n
= 17, 31%) or fibrosis predominant (n = 37, 69%).
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Fig. 4 —64-year-old woman with fibrotic idiopathic interstitial
pneumonia: nonspecific interstitial pneumonia (group 3, fibrotic). Coronal
T2-weighted triple-inversion black blood turbo spin-echo image shows signal
intensity of lesions (arrows) in both lower lobes is similar to that
of adjacent chest wall muscles. Histopathologic examination of biopsy specimen
obtained from left lower lobe disclosed advanced pulmonary fibrosis.
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Qualitative MRI Analyses
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.
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Fig. 5A —55-year-old woman with pattern 1 nonspecific interstitial
pneumonia (group 1, cellular) exhibiting early enhancement and washout.
Transverse high-resolution CT scan (1.25-mm section thickness) at level of
liver dome shows subpleural patchy parenchymal opacities (arrows) in
both lungs.
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Fig. 5B —55-year-old woman with pattern 1 nonspecific interstitial
pneumonia (group 1, cellular) exhibiting early enhancement and washout. Serial
dynamic MR images show early enhancement with delayed washout pattern
(arrow). Biopsy was performed on lesions in left upper and lower
lobes. Pathologic specimens disclosed inflammation-predominant nonspecific
interstitial pneumonia (group 1, cellular).
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Fig. 5C —55-year-old woman with pattern 1 nonspecific interstitial
pneumonia (group 1, cellular) exhibiting early enhancement and washout. Serial
dynamic MR images show early enhancement with delayed washout pattern
(arrow). Biopsy was performed on lesions in left upper and lower
lobes. Pathologic specimens disclosed inflammation-predominant nonspecific
interstitial pneumonia (group 1, cellular).
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Fig. 5D —55-year-old woman with pattern 1 nonspecific interstitial
pneumonia (group 1, cellular) exhibiting early enhancement and washout. Serial
dynamic MR images show early enhancement with delayed washout pattern
(arrow). Biopsy was performed on lesions in left upper and lower
lobes. Pathologic specimens disclosed inflammation-predominant nonspecific
interstitial pneumonia (group 1, cellular).
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Fig. 5E —55-year-old woman with pattern 1 nonspecific interstitial
pneumonia (group 1, cellular) exhibiting early enhancement and washout. Serial
dynamic MR images show early enhancement with delayed washout pattern
(arrow). Biopsy was performed on lesions in left upper and lower
lobes. Pathologic specimens disclosed inflammation-predominant nonspecific
interstitial pneumonia (group 1, cellular).
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Fig. 5F —55-year-old woman with pattern 1 nonspecific interstitial
pneumonia (group 1, cellular) exhibiting early enhancement and washout. Serial
dynamic MR images show early enhancement with delayed washout pattern
(arrow). Biopsy was performed on lesions in left upper and lower
lobes. Pathologic specimens disclosed inflammation-predominant nonspecific
interstitial pneumonia (group 1, cellular).
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Fig. 6A —70-year-old man with pattern 2 usual interstitial pneumonia
exhibiting slight enhancement. Coronal thin-section (2.5-mm section thickness)
CT scan shows subpleural honeycombing and reticulation (arrows) in
both lungs.
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Fig. 6B —70-year-old man with pattern 2 usual interstitial pneumonia
exhibiting slight enhancement. Serial dynamic MR images show slight
enhancement. Biopsy was performed on lesions in right lower lobe. Pathologic
specimens disclosed fibrosis-predominant usual interstitial pneumonia.
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Fig. 6C —70-year-old man with pattern 2 usual interstitial pneumonia
exhibiting slight enhancement. Serial dynamic MR images show slight
enhancement. Biopsy was performed on lesions in right lower lobe. Pathologic
specimens disclosed fibrosis-predominant usual interstitial pneumonia.
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Fig. 6D —70-year-old man with pattern 2 usual interstitial pneumonia
exhibiting slight enhancement. Serial dynamic MR images show slight
enhancement. Biopsy was performed on lesions in right lower lobe. Pathologic
specimens disclosed fibrosis-predominant usual interstitial pneumonia.
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Fig. 6E —70-year-old man with pattern 2 usual interstitial pneumonia
exhibiting slight enhancement. Serial dynamic MR images show slight
enhancement. Biopsy was performed on lesions in right lower lobe. Pathologic
specimens disclosed fibrosis-predominant usual interstitial pneumonia.
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Fig. 6F —70-year-old man with pattern 2 usual interstitial pneumonia
exhibiting slight enhancement. Serial dynamic MR images show slight
enhancement. Biopsy was performed on lesions in right lower lobe. Pathologic
specimens disclosed fibrosis-predominant usual interstitial pneumonia.
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Fig. 7A —48-year-old woman with pattern 3 nonspecific interstitial
pneumonia (group 3) exhibiting delayed persistent enhancement. Transverse
high-resolution CT scan (1.25-mm section thickness) at liver dome level shows
patchy ground-glass opacities (arrows) containing reticulation and
traction bronchiectasis in both lower lobes.
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Fig. 7B —48-year-old woman with pattern 3 nonspecific interstitial
pneumonia (group 3) exhibiting delayed persistent enhancement. Serial dynamic
MR images show delayed persistent enhancement. Biopsy was performed on lesions
in left lower lobe. Pathologic specimens disclosed fibrosis-predominant
nonspecific interstitial pneumonia (group 3).
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Fig. 7C —48-year-old woman with pattern 3 nonspecific interstitial
pneumonia (group 3) exhibiting delayed persistent enhancement. Serial dynamic
MR images show delayed persistent enhancement. Biopsy was performed on lesions
in left lower lobe. Pathologic specimens disclosed fibrosis-predominant
nonspecific interstitial pneumonia (group 3).
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Fig. 7D —48-year-old woman with pattern 3 nonspecific interstitial
pneumonia (group 3) exhibiting delayed persistent enhancement. Serial dynamic
MR images show delayed persistent enhancement. Biopsy was performed on lesions
in left lower lobe. Pathologic specimens disclosed fibrosis-predominant
nonspecific interstitial pneumonia (group 3).
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Fig. 7E —48-year-old woman with pattern 3 nonspecific interstitial
pneumonia (group 3) exhibiting delayed persistent enhancement. Serial dynamic
MR images show delayed persistent enhancement. Biopsy was performed on lesions
in left lower lobe. Pathologic specimens disclosed fibrosis-predominant
nonspecific interstitial pneumonia (group 3).
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Fig. 7F —48-year-old woman with pattern 3 nonspecific interstitial
pneumonia (group 3) exhibiting delayed persistent enhancement. Serial dynamic
MR images show delayed persistent enhancement. Biopsy was performed on lesions
in left lower lobe. Pathologic specimens disclosed fibrosis-predominant
nonspecific interstitial pneumonia (group 3).
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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).
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TABLE 2: Diagnostic Characteristics for Predicting Disease Activity According to
Dynamic MRI Qualitative Criteria (n = 54)
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Quantitative Analysis of Dynamic MRI
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).
Semiquantitative Pathologic Scores, Dynamic MRI Parameters, Clinical Outcome, and Correlation
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).
Discussion
It is important to discriminate between inflammation- and
fibrosis-predominant lesions of IIP because treatment response and long-term
survival rate can be predicted with histologic patterns (inflammation vs
fibrosis) [6,
7]. Although patients with IIP
often are treated with high-dose corticosteroids, such therapies are not
universally effective and are associated with risk. Thus noninvasive imaging
methods, which facilitate differentiation of inflammation- and
fibrosis-predominant lesions of IIP, are needed for treatment decision-making
and for prediction of treatment response.
In this study, qualitative analysis of dynamic T1-weighted 3D turbo
field-echo MR images obtained at 3 T proved helpful for differentiating
inflammation- and fibrosis-predominant lesions. Most (82%, 14 of 17 sites) of
the inflammation-predominant lesions had an early enhancement pattern. Three
inflammation-predominant lesion sites did not have early enhancement on
dynamic MRI. We presume that those lesions were too subtle in terms of density
or too small in extent to be detected as enhancing lesions during visual
assessment of lesions on MR images.
From the practical point of view, visual assessment of dynamic enhancement
pattern is easier than time–intensity curve analysis. Overall, the
presence of a visually noticeable early-enhancing lesion was an accurate
indicator of active disease with high positive and negative predictive values,
82% and 92%, respectively. At time–intensity curve analysis,
inflammation-predominant lesions had a higher percentage signal intensity in
the initial dynamic phase at 1 minute with faster time to peak and slope
enhancement. Fibrosis-predominant lesions had delayed enhancement (positive
percentage signal intensity difference in subtraction of percentage signal
intensity at 1 minute from that at 10 minutes). Therefore, absence of early
enhancement significantly decreases the probability that treatable or
reversible lung disease is present and that corticosteroid therapy probably is
not necessary for these patients.
Gaeta et al. [11] reported
that pulmonary lesions associated with inactive chronic infiltrative lung
disease do not exhibit enhancement but that most (82%, 14 of 17) active
lesions exhibit noticeable enhancement on MR images. This finding was
corroborated in our study. At quantitative analysis we identified early
enhancement with a higher percentage signal intensity at 1 minute and faster
slope of enhancement in the inflammation-predominant group. In our study,
however, the fibrosis-predominant lesions (41%, 15 of 37 sites) exhibited
enhancement in the delayed phase. Owing to the short period (3 minutes) of
dynamic range covered in the previous study, the investigators might have not
noticed the delayed enhancement of fibrotic lung lesions during the late
redistribution phase after IV administration of MRI contrast medium.
The early enhancement pattern of inflammation-predominant lesions on
dynamic MRI may be due to an increased extravascular interstitial space with
abundant inflammatory cell infiltrates or promotion of neovascularization with
increased angiogenesis in those lesions
[27]. Diffusible hydrophilic
low-molecular-weight gadopentetate dimeglumine can freely cross the
interendothelial pores of the microvasculature by diffusing into extravascular
lung spaces and reentering the intravascular space
[28,
29]. If active inflammation is
associated with an increased volume of extravascular interstitial space and
angiogenic activity, net movement of gadopentetate dimeglumine would remain
greater in the extravascular space of the lung interstitium during the early
equilibrium period approximately 3 minutes after contrast injection. In our
study, at pathologic examination, this expected phenomenon of early
enhancement of inflammation-predominant lesions was reflected by the presence
of high scores for interstitial mononuclear cell infiltrates and intraalveolar
macrophages and exudates at the corresponding lesion sites.
Another important pathologic feature was the presence of established
fibrosis in the fibrosis-predominant group. This presence of fibrous tissue
replacing interstitium might have contributed to the destruction of
capillaries and thus impaired washout, resulting in delayed rather than early
enhancement at fibrosis sites on dynamic MRI. Therefore, in our study, the
most reliable MRI finding for predicting the presence of
inflammation-predominant lesions was the presence of early and rapid
enhancement. Moreover, the enhancement rate was found to have a positive
correlation with inflammatory histopathologic score (interstitial mononuclear
cell infiltration, intraalveolar macrophages and exudates) and a negative
correlation with established fibrosis. The extent of enhancement per se did
not contribute measurably to differentiation of inflammation- and
fibrosis-predominant lung lesions because the latter lesions did exhibit
delayed enhancement.
T2-weighted triple-inversion black blood TSE images had fairly good
resolution and contrast for lung imaging with less motion artifact due to
breath-holding, ECG gating, and decreased imaging time. High-signal-intensity
lesions on T2-weighted triple-inversion black blood TSE images may represent
increased water content due to the presence of inflammatory cells and exudates
in the interstitium and alveolar air-spaces. It has been reported
[21] that MRI at 3 T can be
used to detect diffuse pulmonary disease with sensitivity close to that of
helical CT. In our experience
[30] with lung MRI at 3 T, the
characteristics and the extent of parenchymal lesions were discerned with
anatomic detail and without substantial intrinsic or extrinsic motion
artifact.
Our study had several limitations. First, the analyses were executed per
biopsy site. In clinical practice, the unit of disease treatment is the
patient, not the individual lesion. However, our study started with the idea
that in a given patient, pathologic specimens can have heterogeneous results.
Second, the number of lesion sites with active inflammation was relatively
small compared with the number of sites with fibrosis. Third, the patients who
underwent surgical biopsy for IIP were mostly those who had somewhat atypical
presentations of the disease. Patients with the typical clinical presentation
of UIP usually do not undergo surgical biopsy. This fact might have
contributed to selection bias. Fourth, the MRI protocols were designed with a
patient breath-hold. Several patients might have had difficulty holding their
breath, but those difficulties did not cause a crucial artifact.
Assessment of signal intensity on T2-weighted triple-inversion black blood
TSE images and of multiphase dynamic enhancement studies performed with fast
imaging technique (T1-weighted turbo field-echo sequence) at 3-T MRI is useful
for evaluating IIP activity and enables prediction of the histopathologic
features of predominant inflammation and fibrosis.
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Abstract
Introduction
