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Published online before print March 30, 2007, 10.1148/radiol.2432060131
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(Radiology 2007;243:570-577.)
© RSNA, 2007

Thoracic Imaging

Lung Carcinoma: Diffusion-weighted MR Imaging—Preliminary Evaluation with Apparent Diffusion Coefficient1

Munetaka Matoba, MD, Hisao Tonami, MD, Tamaki Kondou, MD, Hajime Yokota, MD, Kotaro Higashi, MD, Hirohisa Toga, MD, and Tutomu Sakuma, MD

1 From the Departments of Radiology (M.M., H. Tonami, T.K., H.Y., K.H.), Internal Medicine (H. Toga), and Thoracic Surgery (T.S.), Kanazawa Medical University, Daigaku 1-1, Uchinada, Kahoku, Ishikawa 920-0293, Japan. From the 2004 RSNA Annual Meeting. Received January 23, 2006; revision requested March 23; revision received June 4; accepted June 21; final version accepted September 18. Address correspondence to M.M. (e-mail: m-matoba{at}kanazawa-med.ac.jp).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Purpose: To prospectively evaluate diffusion-weighted (DW) magnetic resonance (MR) imaging with a split acquisition of fast spin-echo signals for diffusion imaging (SPLICE) sequence for tissue characterization of lung carcinomas by using apparent diffusion coefficients (ADCs).

Materials and Methods: An institutional review board approved this study; informed consent was obtained from patients. Thirty patients (nine women, 21 men; mean age, 68.0 years) with lung carcinoma underwent DW MR imaging with the SPLICE sequence. ADC of each lung carcinoma was calculated from DW MR images obtained with low and high b values. ADCs of lung carcinomas were statistically compared among histologic types. Nine surgically excised lung carcinomas were evaluated for correlation between ADCs and tumor cellularities. Analysis of variance was used to determine changes in ADCs and histologic lung carcinoma types. Spearman rank correlation was calculated between ADCs and tumor cellularities.

Results: ADCs for lung carcinomas were 1.63 x 10–3 mm2/sec ± 0.5 (mean ± standard deviation) for squamous cell carcinoma, 2.12 x 10–3 mm2/sec ± 0.6 for adenocarcinoma, 1.30 x 10–3 mm2/sec ± 0.4 for large-cell carcinoma, and 2.09 x 10–3 mm2/sec ± 0.3 for small-cell carcinoma. ADC of adenocarcinoma was significantly higher than that of squamous cell carcinoma and large-cell carcinoma (P < .05). ADCs were 1.59 x 10–3 mm2/sec ± 0.5 and 1.70 x 10–3 mm2/sec ± 0.4 for moderately and poorly differentiated squamous cell carcinoma, respectively. ADCs were 2.52 x 10–3 mm2/sec ± 0.4 and 1.44 x 10–3 mm2/sec ± 0.3 for well- and poorly differentiated adenocarcinoma, respectively. ADC of well-differentiated adenocarcinoma was significantly higher than that of moderately and poorly differentiated squamous cell carcinoma and poorly differentiated adenocarcinoma (P < .05). With the Spearman rank test, ADCs of lung carcinomas correlated well with tumor cellularities (Spearman coefficient, –0.75; P < .02).

Conclusion: ADCs of lung carcinomas overlap, but ADCs of well-differentiated adenocarcinoma appear to be higher than those of other histologic lung carcinoma types.

© RSNA, 2007


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
The principle of diffusion-weighted (DW) magnetic resonance (MR) imaging exploits the random motion, or so-called brownian movement, of water protons in biologic tissue (1). This motion causes phase dispersion of the spins, resulting in signal loss with the use of diffusion-sensitive sequences (2). This signal loss can be quantified by calculating the apparent diffusion coefficient (ADC), which depends largely on the presence of barriers to diffusion within the water microenvironment, namely, cell membranes and macromolecules (3). DW MR images and ADC values add important information to findings obtained with conventional MR imaging and have been widely used in brain imaging, primarily for the evaluation of acute ischemic stroke, intracranial tumors, and demyelinating disease (4–6).

With the advent of the echo-planar MR imaging technique, DW MR imaging of the abdomen and thoracic cavity has become possible with fast imaging times, which minimize the effects of gross physiologic motion from respiration and cardiac movement (7). The application of DW echo-planar MR imaging has extended to the breast and prostatic regions and allows for differentiation between tumor and normal tissue (8,9). DW echo-planar MR imaging has also been used in the hepatic region to help differentiate between malignant and benign lesions (10). However, DW echo-planar MR imaging is not satisfactory in general because of problems with susceptibility, fat saturation, and spatial resolution.

The split acquisition of fast spin-echo signals for diffusion imaging (SPLICE) sequence is a technique that combines single-shot DW imaging with a modified fast spin-echo acquisition mode (11). In contrast to DW echo-planar MR imaging, the SPLICE sequence works well in the presence of marked macroscopic or microscopic inhomogeneities of the magnetic field and is therefore better suited for thoracic and abdominal imaging (11).

Thus, the purpose of our study was to prospectively evaluate DW MR imaging with a SPLICE sequence for tissue characterization of lung carcinomas by using ADC.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Patients
Our study received institutional review board approval, and all patients provided informed consent. Thirty-two consecutive patients (10 women, 22 men; mean age, 68.7 years; age range, 55–76 years) who met our study criteria and who were suspected of having primary lung carcinoma at chest computed tomography (CT) were referred to undergo MR imaging between March 2002 and March 2004. The entry criteria for patients were as follows: (a) At thin-section CT, the pulmonary nodule appeared as a solid opacity without an air-containing area and/or the percentage of the extent of ground-glass opacity within the lesion was estimated to be less than 50%. (b) The largest diameter of the pulmonary nodule was larger than 2.0 cm. (c) Surgical resection or biopsy of the lesion had been planned.

Pathologic confirmation was on the basis of surgical resection findings in 11 patients and on the basis of transbronchial or percutaneous biopsy findings in 21 patients. These 21 patients did not undergo surgical resection because they were deemed medically inoperable owing to comorbidities and surgical risk. Diagnoses were two benign lesions, including one necrotizing epithelioid granuloma and one progressive massive fibrosis, and 30 lung carcinomas, including 13 squamous cell carcinomas (eight moderately differentiated and five poorly differentiated), 11 adenocarcinomas (seven well differentiated and four poorly differentiated), three large-cell carcinomas, and three small-cell carcinomas. The mean size was 3.1 cm (range, 2.1–4.2 cm) for squamous cell carcinoma, 2.3 cm (range, 2.0–3.4 cm) for adenocarcinoma, 5.7 cm (range, 4.7–6.4 cm) for large-cell carcinoma, and 2.8 cm (range, 2.2–3.6 cm) for small-cell carcinoma. For the 30 patients with lung carcinoma (our final study group: mean age, 68.0 years; nine women, 21 men), pathologic confirmation was based on surgical resection findings in nine cases, including three squamous cell carcinomas (all moderately differentiated), five adenocarcinomas (three well differentiated and two poorly differentiated), and one large-cell carcinoma.

MR Imaging: Patients and Phantoms
All MR examinations were performed with a 1.5-T clinical imager (Magnetom Vision; Siemens, Erlangen, Germany) with a maximum gradient strength of 25 mT/m and rise time of 600 µsec by using a body phased-array coil. Patients were in the supine position throughout the examination. Prior to DW MR imaging, T1- and T2-weighted images were obtained in the transverse plane in each patient. T1-weighted spin-echo images were obtained with the following parameters: repetition time msec/echo time msec, 720/20; number of signals acquired, six; matrix, 192 x 256; field of view, 32 cm; and section thickness, 8 mm. T2-weighted fast spin-echo images were obtained with the following parameters: 6700/130; echo train length, 15; number of signals acquired, four; matrix, 192 x 256; field of view, 32 cm; and section thickness, 8 mm. These images were inspected initially to define section locations for the DW MR images of the pulmonary lesion. The section locations for the DW MR images were defined by using accepted criteria (section locations covering the pulmonary lesion) by two radiologists (M.M., with 10 years of experience in clinical MR imaging; K.H., with 15 years of experience in chest imaging) in consensus.

DW MR images were acquired by using an electrocardiographically gated SPLICE sequence. Cardiac motion is large compared with molecular brownian motion; this discrepancy leads to signal voids on the DW MR image. This in turn leads to artifactually high estimates of the ADC. With the electrocardiographically gated SPLICE sequence, a trigger delay of 100 msec (12) was established between the R peak in the cardiac cycle and a 90° excitation radiofrequency pulse. The excitation for consecutive sections was triggered to every third R peak in the cardiac cycle. On the basis of T1- and T2-weighted images, DW MR imaging examinations were performed only in the section locations of the pulmonary lesion in the transverse plane during breath holding. DW MR images were obtained with b values of 68.46 and 577.05 sec/mm2. The components of the applied gradients for diffusion weighting, which consisted of three orthogonal gradients, were equal in read, phase, and section orientation to obtain maximum total gradient strength. The trace DW images to minimize the effect of diffusion anisotropy were then obtained. With the SPLICE sequence, DW half-Fourier single-shot turbo spin-echo imaging was used in this study; therefore, the data were collected in half-Fourier fashion. A total of 102 echoes were acquired at each examination for each section with an echo spacing of 5.9 msec, and a 192 x 256 viewing matrix was reconstructed. Other parameters were as follows: echo time, 65 msec; effective band width, 650 Hz/pixel; field of view, 32 cm; section thickness, 6 mm; and number of signals acquired, one. Acquisition time for each section was in subseconds (range, 635–745 msec). Imaging time was 16–27 seconds, depending on the number of sections covering the lung carcinoma (seven to 10 sections) and patient heart rate.

Further, to validate our system, a preliminary phantom study with one 1.5-cm-diameter plastic tube filled with water and another filled with acetone was conducted, and ADC values of the two substances were calculated at ambient room temperature (21°C) (M.M., H.Y.).

Image Analysis
All DW MR images were analyzed in consensus by two experienced radiologists (M.M., T.K., each with 6 years of experience in clinical MR imaging). DW MR images were analyzed qualitatively by focusing on the signal intensity of the lung carcinomas, which was classified by using visual assessment of hypointensity or hyperintensity in comparison with the signal intensity of adjacent skeletal muscle. The comparison of signal intensities on DW MR images among histologic types of lung carcinoma then was performed. ADC values were measured for all lung carcinomas. ADC values were calculated with a linear regression analysis of the natural log of signal intensity versus the gradient factor according to the following equation: ADC = –[ln (Sh/Sl)]/(bh – bl).

Sh and Sl were the signal intensities in the region of interest obtained with two different gradient factors (bh and bl). In this study, bh was 577.05 sec/mm2 and bl was 68.46 sec/mm2. A region of interest with a diameter of approximately 1.0 cm was positioned for the measurement of ADC in each lung carcinoma. Because the size of the lung carcinomas included in our study was more than 2.0 cm, the region of interest could be placed on the solid area of the lung carcinoma, with exclusion of any necrotic area. If there seemed to be no necrotic area, the region of interest was placed on the center of the lung carcinoma. Mean ADC values were then obtained. There were no motion artifacts that resulted in poor image quality or instances of image distortion due to susceptibility.

Analysis of Tumor Cellularity
Nine surgically excised lung carcinomas were analyzed for tumor cellularity. Analysis of tumor cellularity was performed by using a method similar to the one used by Sugahara et al (13). Initially, three slices (counterstained with hematoxylin-eosin) were obtained from different regions in each tumor. Two fields of view (original magnification, x200) were chosen by one histopathologist (with 8 years of experience in histopathology) from each slice and scanned into a personal computer for the analysis of tumor cellularity. The scanned images were converted into gray scale by setting the image mode to gray scale. Tumor cellularity was defined by using U.S. National Institutes of Health Images. The threshold was defined as the pixel intensity value below which the tissue on the image would be categorized as tumor cell nuclei. Tumor cell nuclei were identified by low pixel intensities. However, to minimize individual variation, the intensity values below which the tissue would be categorized as tumor cells were carefully chosen by one radiologist (H.Y., with 10 and 4 years of experience in clinical MR imaging and histopathology, respectively) three times in each specimen. Finally, mean tumor cellularity was calculated according to the predefined threshold by dividing the total area of tumor cell nuclei by the area of the histologic slice.

Statistical Analysis
Statistical analyses were performed by using statistical software (SAS, version 8.0; SAS, Cary, NC). To compare mean ADC values among histologic types of lung carcinoma and cell differentiation types of squamous cell carcinoma and adenocarcinoma, analysis of variance was used. The post hoc hypothesis testing was performed according to the Fisher protected least significant difference method. In addition, Spearman rank correlation coefficients were calculated to evaluate the correlation between mean ADC values and tumor cellularities of lung carcinomas. A P value of less than .05 was considered to indicate a statistically significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Phantom Studies
ADC values of distilled water and acetone were found to be 2.56 x 10–3 mm2/sec and 4.79 x 10–3 mm2/sec, respectively, at room temperature (21°C). There was no marked difference between our measurement values and already known diffusion coefficients of distilled water (2.26 x 10–3 mm2/sec) and acetone (4.58 x 10–3 mm2/sec) (7,14); however, our measurements tended to be higher.

Comparison of Signal Intensities and ADC Values among Histologic Types of Lung Carcinoma
All lung carcinomas were detected as hyperintense lesions in relation to adjacent skeletal muscle on DW images obtained with a b value of 68.46 sec/mm2. On DW images obtained with a b value of 577.05 sec/mm2, one of seven cases of well-differentiated adenocarcinoma and other histologic types of lung carcinoma were hyperintense in relation to adjacent skeletal muscle (Fig 1). However, six of seven cases of well-differentiated adenocarcinoma were remarkably hypointense in comparison with adjacent skeletal muscle (Fig 2, Table 1).


Figure 1A
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  		Figure 1a: Transverse MR images in 77-year-old man with moderately differentiated squamous cell carcinoma. (a) T1-weighted spin-echo image (720/20) shows nodule with intermediate signal intensity, the same as that of skeletal muscle. (b) T2-weighted fast spin-echo image (6700/130) shows hyperintense nodule in relation to skeletal muscle. (c) DW image obtained with diffusion gradient of 68.46 sec/mm2 shows hyperintense nodule in relation to skeletal muscle. (d) On DW image obtained with diffusion gradient of 577.05 sec/mm2, nodule is hyperintense in relation to skeletal muscle. ADC was 1.52 x 10–3 mm2/sec. Histologic specimen of nodule (not shown) had high cellularity (histologic cellularity = 31.3%).

 

Figure 1B
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  		Figure 1b: Transverse MR images in 77-year-old man with moderately differentiated squamous cell carcinoma. (a) T1-weighted spin-echo image (720/20) shows nodule with intermediate signal intensity, the same as that of skeletal muscle. (b) T2-weighted fast spin-echo image (6700/130) shows hyperintense nodule in relation to skeletal muscle. (c) DW image obtained with diffusion gradient of 68.46 sec/mm2 shows hyperintense nodule in relation to skeletal muscle. (d) On DW image obtained with diffusion gradient of 577.05 sec/mm2, nodule is hyperintense in relation to skeletal muscle. ADC was 1.52 x 10–3 mm2/sec. Histologic specimen of nodule (not shown) had high cellularity (histologic cellularity = 31.3%).

 

Figure 1C
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  		Figure 1c: Transverse MR images in 77-year-old man with moderately differentiated squamous cell carcinoma. (a) T1-weighted spin-echo image (720/20) shows nodule with intermediate signal intensity, the same as that of skeletal muscle. (b) T2-weighted fast spin-echo image (6700/130) shows hyperintense nodule in relation to skeletal muscle. (c) DW image obtained with diffusion gradient of 68.46 sec/mm2 shows hyperintense nodule in relation to skeletal muscle. (d) On DW image obtained with diffusion gradient of 577.05 sec/mm2, nodule is hyperintense in relation to skeletal muscle. ADC was 1.52 x 10–3 mm2/sec. Histologic specimen of nodule (not shown) had high cellularity (histologic cellularity = 31.3%).

 

Figure 1D
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  		Figure 1d: Transverse MR images in 77-year-old man with moderately differentiated squamous cell carcinoma. (a) T1-weighted spin-echo image (720/20) shows nodule with intermediate signal intensity, the same as that of skeletal muscle. (b) T2-weighted fast spin-echo image (6700/130) shows hyperintense nodule in relation to skeletal muscle. (c) DW image obtained with diffusion gradient of 68.46 sec/mm2 shows hyperintense nodule in relation to skeletal muscle. (d) On DW image obtained with diffusion gradient of 577.05 sec/mm2, nodule is hyperintense in relation to skeletal muscle. ADC was 1.52 x 10–3 mm2/sec. Histologic specimen of nodule (not shown) had high cellularity (histologic cellularity = 31.3%).

 

Figure 2A
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  		Figure 2a: Transverse MR images in 59-year-old woman with well-differentiated adenocarcinoma. (a) T1-weighted spin-echo image (720/20) shows nodule with intermediate signal intensity, the same as that of skeletal muscle. (b) T2-weighted fast spin-echo image (6700/130) shows hyperintense nodule in relation to skeletal muscle. (c) DW image obtained with diffusion gradient of 68.46 sec/mm2 shows hyperintense nodule in relation to skeletal muscle. (d) On DW image with diffusion gradient of 577.05 sec/mm2, nodule is hypointense compared with skeletal muscle. ADC was 2.57 x 10–3 mm2/sec. Histologic specimen of nodule (not shown) had low cellularity (histologic cellularity = 7.7%).

 

Figure 2B
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  		Figure 2b: Transverse MR images in 59-year-old woman with well-differentiated adenocarcinoma. (a) T1-weighted spin-echo image (720/20) shows nodule with intermediate signal intensity, the same as that of skeletal muscle. (b) T2-weighted fast spin-echo image (6700/130) shows hyperintense nodule in relation to skeletal muscle. (c) DW image obtained with diffusion gradient of 68.46 sec/mm2 shows hyperintense nodule in relation to skeletal muscle. (d) On DW image with diffusion gradient of 577.05 sec/mm2, nodule is hypointense compared with skeletal muscle. ADC was 2.57 x 10–3 mm2/sec. Histologic specimen of nodule (not shown) had low cellularity (histologic cellularity = 7.7%).

 

Figure 2C
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  		Figure 2c: Transverse MR images in 59-year-old woman with well-differentiated adenocarcinoma. (a) T1-weighted spin-echo image (720/20) shows nodule with intermediate signal intensity, the same as that of skeletal muscle. (b) T2-weighted fast spin-echo image (6700/130) shows hyperintense nodule in relation to skeletal muscle. (c) DW image obtained with diffusion gradient of 68.46 sec/mm2 shows hyperintense nodule in relation to skeletal muscle. (d) On DW image with diffusion gradient of 577.05 sec/mm2, nodule is hypointense compared with skeletal muscle. ADC was 2.57 x 10–3 mm2/sec. Histologic specimen of nodule (not shown) had low cellularity (histologic cellularity = 7.7%).

 

Figure 2D
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  		Figure 2d: Transverse MR images in 59-year-old woman with well-differentiated adenocarcinoma. (a) T1-weighted spin-echo image (720/20) shows nodule with intermediate signal intensity, the same as that of skeletal muscle. (b) T2-weighted fast spin-echo image (6700/130) shows hyperintense nodule in relation to skeletal muscle. (c) DW image obtained with diffusion gradient of 68.46 sec/mm2 shows hyperintense nodule in relation to skeletal muscle. (d) On DW image with diffusion gradient of 577.05 sec/mm2, nodule is hypointense compared with skeletal muscle. ADC was 2.57 x 10–3 mm2/sec. Histologic specimen of nodule (not shown) had low cellularity (histologic cellularity = 7.7%).

 

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  		Table 1. Comparison of Signal Intensities on DW MR Images among Histologic Types of Lung Carcinoma

 
It was possible to obtain ADC values in all patients. The calculated mean ADC values (Fig 3) for the lung carcinomas were as follows: 1.63 x 10–3 mm2/sec ± 0.5 (mean ± standard deviation) for squamous cell carcinoma, 2.12 ± 0.6 x 10–3 mm2/sec for adenocarcinoma, 1.30 x 10–3 mm2/sec ± 0.4 for large-cell carcinoma, and 2.09 x 10–3 mm2/sec ± 0.3 for small-cell carcinoma. Mean ADC value of adenocarcinoma was significantly higher than those of squamous cell carcinoma and large-cell carcinoma (P < .05 for both) (Table 2).


Figure 3
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  		Figure 3: Scatterplots of ADC values obtained in histologic types of lung carcinoma. ADC values of lung carcinomas overlap among histologic types. Adeno = adenocarcinoma, LCC = large cell carcinoma, SCC = small cell carcinoma, SqCC = squamous cell carcinoma.

 

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  		Table 2. Comparison of ADCs among Histologic Types of Lung Carcinoma

 
With regard to ADC values obtained with different degrees of cell differentiation in squamous cell carcinoma and adenocarcinoma (Fig 4), mean ADC values were as follows: 1.59 x 10–3 mm2/sec ± 0.5 and 1.70 x 10–3 mm2/sec ± 0.4 for moderately and poorly differentiated squamous cell carcinoma, respectively, and 2.52 x 10–3 mm2/sec ± 0.4 and 1.44 x 10–3 mm2/sec ± 0.3 for well- and poorly differentiated adenocarcinoma, respectively. The mean ADC value of well-differentiated adenocarcinoma was significantly higher than those of moderately and poorly differentiated squamous cell carcinoma and poorly differentiated adenocarcinoma (P < .05 for each) (Table 3).


Figure 4
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  		Figure 4: Scatterplots of ADC values obtained in degrees of cell differentiation in squamous cell carcinoma and adenocarcinoma. Although overlaps exist among ADC values of degrees of cell differentiation in squamous cell carcinoma and adenocarcinoma, ADC values of well-differentiated adenocarcinoma tend to be higher. Adeno (poorly) = poorly differentiated adenocarcinoma, Adeno (well) = well-differentiated adenocarcinoma, SqCC (moderately) = moderately differentiated squamous cell carcinoma, SqCC (poorly) = poorly differentiated squamous cell carcinoma.

 

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  		Table 3. Comparison of ADCs among Degrees of Cell Differentiation in Carcinomas

 
Relationship of Tumor Cellularity to Mean ADC Values
We performed correlation analysis between mean ADC values and tumor cellularities in nine cases of lung carcinoma diagnosed by using surgical resection findings. By using the Spearman rank test, we found a significant correlation between them (Spearman coefficient, –0.75; P < .02) (Fig 5). Well-differentiated adenocarcinomas have lower cellularity and higher ADC values than poorly differentiated adenocarcinomas and other histologic types of lung carcinoma.


Figure 5
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  		Figure 5: Graph shows correlation between tumor cellularity and mean ADC values of lung carcinomas in cases of surgical resection. Significant negative linear correlation was found between tumor cellularity and mean ADC (Spearman coefficient, –0.75; P < .02). Adeno (poorly) = poorly differentiated adenocarcinoma, Adeno (well) = well-differentiated adenocarcinoma, SqCC (moderately) = moderately differentiated squamous cell carcinoma, SqCC (poorly) = poorly differentiated squamous cell carcinoma.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 References
 
The ADC value refers to the specific diffusion capacity of a biologic tissue. ADC value depends largely on the presence of barriers to diffusion within the water microenvironment, namely, cell membranes, tight junctions, fibers, macromolecules, and cell organelles (3). Consequently, compartments within different cellular structures may exhibit dissimilar ADC values, and the ADC value can therefore aid in determining different tissue types and tissue characteristics (15,16).

The ADC value is estimated to be lower in viable tumor tissue with densely packed diffusion-hindering obstacles than in tissue with less densely packed obstacles, such as tumor necrosis and benign tissue (17). Sugahara et al (13) have reported that the ADC value of gliomas significantly correlates with tumor cellularity and that ADC values of high-grade gliomas are significantly lower than those of low-grade gliomas. In addition, Guo et al (8) have revealed that tumor cellularity has a significant influence on ADC values obtained in both benign and malignant breast tumors. Therefore, tumor cellularity may be an important factor influencing ADC values in viable tumor tissue.

In our study, the mean ADC value of adenocarcinoma was significantly higher than that of squamous cell carcinoma and large-cell carcinoma; in particular, the mean ADC value of well-differentiated adenocarcinoma was significantly higher than that of poorly differentiated adenocarcinoma and squamous cell carcinoma. In addition, a negative correlation was found between mean ADC values of lung carcinomas and tumor cellularity. Histologically, well-differentiated adenocarcinoma characteristically shows a replacement growth pattern in which cylindric tumor cells grow on the walls of preexisting alveoli, with preservation of the underlying architecture of the lung (18), whereas poorly differentiated adenocarcinoma and squamous cell carcinoma show a largely solid growth pattern, with malignant cells proliferating compressively and expansively without a replacement growth pattern (19). Therefore, tumor cellularity of well-differentiated adenocarcinoma may be low in comparison with that of poorly differentiated adenocarcinoma and squamous cell carcinoma, and consequently, ADC values of well-differentiated adenocarcinoma may be higher than those of poorly differentiated adenocarcinoma and squamous cell carcinoma.

ADC values of lung carcinomas seem to be influenced by not only tumor cellularity but also other factors. In our study, although the patient population was relatively small, the mean ADC value of small-cell carcinoma tended to be higher than that of squamous cell carcinoma and large-cell carcinoma. The tumor cellularity of small-cell carcinoma seemed to be relatively high, however, and its ADC values tended to be higher in our study. Herneth et al (17) have shown that tissue ADC is determined by cell density and necrosis is characterized by increased water diffusivity, which means that changes in the ADC are observed before changes on histologic slices and T2-weighted images. Therefore, in small-cell carcinoma with a relatively high ADC value, the degree of necrosis and/or microstructural change that precedes necrosis, including in tumor tissue, seem to be a factor that influences ADC values. However, further studies involving minute comparison of histologic slices with DW images are needed to elucidate the factors influencing ADC values of lung carcinomas.

In this study, we selected relatively low b values to obtain DW MR images of lung carcinomas. If high b values (<1200 sec/mm2) were used for lung DW MR images, image quality would be greatly diminished because the T2 time of the lung field would be very short. We were able to obtain good image quality in our study, but the ADC measurements were problematic in that low b values were used when evaluating ADC values. ADC values tended to be higher when low b values were used, because ADC values are greatly influenced by tissue perfusion and T2 time. In our phantom studies, ADC values of distilled water and acetone tended to be higher than already known ADC values for distilled water and acetone. Therefore, ADC values of lung carcinomas measured in our study generally tended to be higher.

Results of studies (20) have shown that adenocarcinoma has become the most common type of lung carcinoma. Although bronchioloalveolar carcinoma was not included in our study, we were able to evaluate ADC values of adenocarcinoma at CT as corresponding to solid opacity without air-containing areas and/or to a percentage of the extent of ground-glass opacity within the lesion of less than 50%. Our results show that ADC values of well-differentiated adenocarcinoma are significantly higher than those of poorly differentiated adenocarcinoma. Consequently, DW MR imaging may provide useful and interesting information in distinguishing adenocarcinomas.

Our study had limitations. First, the patient population was relatively small, and patient selection was biased by the entry criteria being based on CT findings. Patients who had pulmonary nodules with air-containing areas and/or ground-glass opacity areas that extended to more than 50% of the lesion were excluded from our study. Air-containing areas within the pulmonary nodule could be considered to influence the measurement of ADC values because of inhomogeneities of the magnetic field. Further studies with a large number of patients without potential selection bias are needed. Second, surgical tumor resection in all patients would be required for ideal evaluation of correlation of ADC values with tumor cellularity, but this was not clinically warranted for all patients in our study. Nevertheless, surgical tumor resection findings in nine patients showed that ADC values of lung carcinomas correlated well with tumor cellularity.

On the basis of our preliminary study results, we conclude that although there was an overlap of ADC values among the histologic types of lung carcinoma, ADC values of well-differentiated adenocarcinoma appear to be higher than those of other histologic types of lung carcinoma. In addition, a negative correlation was found between ADC values of lung carcinomas and corresponding tumor cellularities. Consequently, ADC values of lung carcinomas could be considered difficult to use as a differentiating parameter among the histologic types of lung carcinoma. However, in adenocarcinoma, ADC values might be an interesting parameter for distinguishing the degree of cell differentiation causing the difference in tumor cellularity. Clinical experience with our method is still preliminary, and further studies are required to validate our results and to better elucidate the possible clinical applications of our technique.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
References
 


   FOOTNOTES
 

Abbreviations: ADC = apparent diffusion coefficient • DW = diffusion weighted • SPLICE = split acquisition of fast spin-echo signals for diffusion imaging

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, M.M., H. Tonami; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, M.M., T.K., H. Toga, T.S.; clinical studies, M.M., H. Tonami, T.K., H.Y., H. Toga, T.S.; experimental studies, M.M., H.Y.; statistical analysis, M.M., H.Y., K.H.; and manuscript editing, M.M., H. Tonami, K.H.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 

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