ORIGINAL RESEARCH
Diffusion Kurtosis Imaging of the Pancreas for the Assessment of HbA1c Levels Yoshifumi Noda, MD,1 Masayuki Kanematsu, MD,1,2* Satoshi Goshima, MD, PhD,1 Yukio Horikawa, MD, PhD,3 Jun Takeda, MD, PhD,3 Hiroshi Kondo, MD,1 Haruo Watanabe, MD,1 Hiroshi Kawada, MD,1 Nobuyuki Kawai, MD,1 Yukichi Tanahashi, MD,1 and Kyongtae T Bae, MD, PhD4 Purpose: To evaluate the feasibility of diffusion kurtosis (DK) imaging of the pancreas for the assessment of hemoglobin (Hb) A1c values. Materials and Methods: Our Institutional Review Board approved this prospective study and written informed consent was obtained. In all, 102 consecutive patients with suspected pancreatic disease underwent magnetic resonance imaging (MRI), including DK imaging. Patients were classified into three groups according to American Diabetes Association criteria: HbA1c < 5.7% (group 1), 5.7% HbA1c < 6.5% (group 2), and HbA1c 6.5% (group 3). Mean kurtosis (MK) and apparent diffusion coefficient (ADC) of pancreatic parenchyma were computed. MRI measurements and HbA1c values were then compared. Results: HbA1c values positively correlated with MK (r 5 0.66, P < 0.0001). Group 3 was significantly (P < 0.05) higher (P < 0.05) in MK than groups 1 and 2. The sensitivity, specificity, and area under the ROC curve of the MK for the detection of group 3 were 90%, 88%, and 0.92, respectively. Conclusion: The MK measurement on DK imaging of the pancreas could be a potential biomarker for assessing HbA1c level. J. MAGN. RESON. IMAGING 2016;43:159–165.
I
n 2012, 29.1 million Americans, or 9.3% of the population, were estimated to have diabetes, and 86 million Americans aged 20 and older to have prediabetes.1 In particular, the prevalence of type 2 diabetes mellitus is increasing due to population growth, aging, urbanization, increasing obesity, and decreasing physical activity. Patients with diabetes may present with pancreatic fibrosis and atrophy due to glandular replacement by connective tissue and round cells.2 Thus, noninvasive imaging evaluation of the degree of pancreatic fibrosis and atrophy could play a role in the assessment of the extent of disease involvement. Magnetic resonance imaging (MRI) has been used for the evaluation of patients with pancreatic diseases. A previous study reported that the T1-weighted signal intensity of
pancreatic parenchyma relative to liver parenchyma declines in the patients with type 2 diabetes.2 With the development of a parallel encoding technique yielding high image quality, diffusion-weighted (DW) imaging has been incorporated in routine MRI protocols to enhance the differentiation of pancreatic malignant and benign lesions or to evaluate pancreatic parenchymal fibrosis.3,4 Previous studies demonstrated that the DW signal and apparent diffusion coefficient (ADC) values could be influenced not only by molecular diffusion but also microcirculation or blood perfusion. The microcirculation or perfusion effects could be distinguished from true tissue diffusion by using sufficient b values sampling and a biexponential curve fit analysis along with an intravoxel incoherent motion
View this article online at wileyonlinelibrary.com. DOI: 10.1002/jmri.24982 Received Jan 15, 2015, and in revised form Jun 2, 2015. Accepted for publication Jun 3, 2015. *Address reprint requests to: M.K., Department of Radiology and Radiology Services, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194, Japan. E-mail: [email protected] From the 1Department of Radiology, Gifu University Hospital, Gifu, Japan; 2Department of Radiology Services, Gifu University Hospital, Gifu, Japan; Department of Diabetes and Endocrinology, Gifu University Hospital, Gifu, Japan; and 4Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
3
C 2015 Wiley Periodicals, Inc. V 159
Journal of Magnetic Resonance Imaging
FIGURE 1: Flow diagram of the study enrollment population.
(IVIM) model.5,6 On the other hand, diffusion kurtosis (DK) imaging is a diffusion-weighted imaging model representing non-Gaussian diffusion of water molecules. NonGaussian water diffusion likely reflects the effect of tissue complexity on the distribution of water molecules, in particular, the presence of microstructural components such as cell membranes and organelles.7,8 Recently, several studies evaluated the clinical applications of DK imaging in the brain,9,10 prostate,11 and liver.12 Thus, the purpose of this study was to evaluate the feasibility of DK imaging of the pancreas for the assessment of hemoglobin (Hb) A1c values.
Materials and Methods Patients This prospective study was approved by our Institutional Review Board and written informed consent was obtained from all patients. Between January 2012 and December 2012, 123 consecutive patients suspected of having pancreatic disease based on clinical history or previously performed computed tomography (CT) underwent MRI. Twenty-one of the 123 patients were excluded because of severe pancreatic parenchymal atrophy in which the radiologists could not place a circular region-of-interest (ROI) cursor (at least 50 mm2) (n 5 12), autoimmune pancreatitis (n 5 3), pancreatic adenocarcinoma (n 5 2), gastrinoma (n 5 2), unstable breath holding (n 5 1), and post-pancreatoduodenectomy (n 5 1). Thus, the remaining 102 patients (mean age, 66.9 6 10.9 years; age range, 18-87 years), including 62 men (mean age, 68.8 6 8.0 years; age range, 49–82 years) and 40 women (mean age, 63.9 6 13.9 years; age range, 18–87 years) were included in our study (Fig. 1). Among the 102 patients, the diagnosis was intraductal papillary mucinous carcinoma in 24 patients, pancreatic divisum in three, and chronic pancreatitis in two. Patients were 160
classified into three groups based on the American Diabetes Association (ADA) criteria using HbA1c values,13 for which we calculated the averaged casual HbA1c value of up to three times measurements before or after MR examination: low HbA1c level, HbA1c
Diffusion Kurtosis Imaging of the Pancreas for the Assessment of HbA1c Levels Yoshifumi Noda, MD,1 Masayuki Kanematsu, MD,1,2* Satoshi Goshima, MD, PhD,1 Yukio Horikawa, MD, PhD,3 Jun Takeda, MD, PhD,3 Hiroshi Kondo, MD,1 Haruo Watanabe, MD,1 Hiroshi Kawada, MD,1 Nobuyuki Kawai, MD,1 Yukichi Tanahashi, MD,1 and Kyongtae T Bae, MD, PhD4 Purpose: To evaluate the feasibility of diffusion kurtosis (DK) imaging of the pancreas for the assessment of hemoglobin (Hb) A1c values. Materials and Methods: Our Institutional Review Board approved this prospective study and written informed consent was obtained. In all, 102 consecutive patients with suspected pancreatic disease underwent magnetic resonance imaging (MRI), including DK imaging. Patients were classified into three groups according to American Diabetes Association criteria: HbA1c < 5.7% (group 1), 5.7% HbA1c < 6.5% (group 2), and HbA1c 6.5% (group 3). Mean kurtosis (MK) and apparent diffusion coefficient (ADC) of pancreatic parenchyma were computed. MRI measurements and HbA1c values were then compared. Results: HbA1c values positively correlated with MK (r 5 0.66, P < 0.0001). Group 3 was significantly (P < 0.05) higher (P < 0.05) in MK than groups 1 and 2. The sensitivity, specificity, and area under the ROC curve of the MK for the detection of group 3 were 90%, 88%, and 0.92, respectively. Conclusion: The MK measurement on DK imaging of the pancreas could be a potential biomarker for assessing HbA1c level. J. MAGN. RESON. IMAGING 2016;43:159–165.
I
n 2012, 29.1 million Americans, or 9.3% of the population, were estimated to have diabetes, and 86 million Americans aged 20 and older to have prediabetes.1 In particular, the prevalence of type 2 diabetes mellitus is increasing due to population growth, aging, urbanization, increasing obesity, and decreasing physical activity. Patients with diabetes may present with pancreatic fibrosis and atrophy due to glandular replacement by connective tissue and round cells.2 Thus, noninvasive imaging evaluation of the degree of pancreatic fibrosis and atrophy could play a role in the assessment of the extent of disease involvement. Magnetic resonance imaging (MRI) has been used for the evaluation of patients with pancreatic diseases. A previous study reported that the T1-weighted signal intensity of
pancreatic parenchyma relative to liver parenchyma declines in the patients with type 2 diabetes.2 With the development of a parallel encoding technique yielding high image quality, diffusion-weighted (DW) imaging has been incorporated in routine MRI protocols to enhance the differentiation of pancreatic malignant and benign lesions or to evaluate pancreatic parenchymal fibrosis.3,4 Previous studies demonstrated that the DW signal and apparent diffusion coefficient (ADC) values could be influenced not only by molecular diffusion but also microcirculation or blood perfusion. The microcirculation or perfusion effects could be distinguished from true tissue diffusion by using sufficient b values sampling and a biexponential curve fit analysis along with an intravoxel incoherent motion
View this article online at wileyonlinelibrary.com. DOI: 10.1002/jmri.24982 Received Jan 15, 2015, and in revised form Jun 2, 2015. Accepted for publication Jun 3, 2015. *Address reprint requests to: M.K., Department of Radiology and Radiology Services, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194, Japan. E-mail: [email protected] From the 1Department of Radiology, Gifu University Hospital, Gifu, Japan; 2Department of Radiology Services, Gifu University Hospital, Gifu, Japan; Department of Diabetes and Endocrinology, Gifu University Hospital, Gifu, Japan; and 4Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
3
C 2015 Wiley Periodicals, Inc. V 159
Journal of Magnetic Resonance Imaging
FIGURE 1: Flow diagram of the study enrollment population.
(IVIM) model.5,6 On the other hand, diffusion kurtosis (DK) imaging is a diffusion-weighted imaging model representing non-Gaussian diffusion of water molecules. NonGaussian water diffusion likely reflects the effect of tissue complexity on the distribution of water molecules, in particular, the presence of microstructural components such as cell membranes and organelles.7,8 Recently, several studies evaluated the clinical applications of DK imaging in the brain,9,10 prostate,11 and liver.12 Thus, the purpose of this study was to evaluate the feasibility of DK imaging of the pancreas for the assessment of hemoglobin (Hb) A1c values.
Materials and Methods Patients This prospective study was approved by our Institutional Review Board and written informed consent was obtained from all patients. Between January 2012 and December 2012, 123 consecutive patients suspected of having pancreatic disease based on clinical history or previously performed computed tomography (CT) underwent MRI. Twenty-one of the 123 patients were excluded because of severe pancreatic parenchymal atrophy in which the radiologists could not place a circular region-of-interest (ROI) cursor (at least 50 mm2) (n 5 12), autoimmune pancreatitis (n 5 3), pancreatic adenocarcinoma (n 5 2), gastrinoma (n 5 2), unstable breath holding (n 5 1), and post-pancreatoduodenectomy (n 5 1). Thus, the remaining 102 patients (mean age, 66.9 6 10.9 years; age range, 18-87 years), including 62 men (mean age, 68.8 6 8.0 years; age range, 49–82 years) and 40 women (mean age, 63.9 6 13.9 years; age range, 18–87 years) were included in our study (Fig. 1). Among the 102 patients, the diagnosis was intraductal papillary mucinous carcinoma in 24 patients, pancreatic divisum in three, and chronic pancreatitis in two. Patients were 160
classified into three groups based on the American Diabetes Association (ADA) criteria using HbA1c values,13 for which we calculated the averaged casual HbA1c value of up to three times measurements before or after MR examination: low HbA1c level, HbA1c
