Pancreatic triacylglycerol distribution in type 2 diabetes. Reply to Hollingsworth K. G., Al Mrabeh A., Steven S. et al [letter].

To the Editor: We welcome the comments of Hollingsworth et al [1], as the role of pancreas fat content in type 2 diabetes has become a hotly debated issue with diverse non-invasive measurement techniques providing seemingly contradictory results [2]. Although several fat/water imaging techniques have been proposed for assessing pancreatic fat content, including 2-point or multi-echo DIXON [3, 4] and fat-selective imaging techniques [5, 6], there is still no consensus or agreement on what constitutes a valid clinical measurement technique for non-invasive assessment of pancreatic fat. Here we respond to the issues raised and provide data comparing the 2-point 3D modified DIXON (mDIXON) method used in our publication [2] with the 3-point 2DDIXONmethod used by Hollingsworth et al [4]. We also demonstrate the importance of using noise bias correction when measuring pancreas fat. The first issue raised is that the 2-point mDIXON method yielded negative values for the fat fraction in the pancreas, which could indicate poor performance of the method.We have validated the 2-point mDIXONmethod in vitro using fat–water phantoms and in vivo by comparing with proton magnetic resonance spectroscopy (H-MRS) measurements [7]. In addition, as already demonstrated [2], the reproducibility of the 2-point mDIXON method was comparable to that of H-MRS. The negative pancreas fat values are likely to be the result of using a noise bias correction algorithm called lowfat Philips Research Integrated Development Environment (LF-PRIDE) (Philips, Best, the Netherlands), which seemingly produces a more Gaussian noise distribution, which therefore results in statistically valid negative values. The noise distribution without noise bias correction is Rician, i.e. there are no negative values, which can lead to artificially high fat fractions when using DIXON techniques [8]. The second issue raised by Hollingsworth et al is that we reported no fat within pancreatic parenchymal tissue, which contradicts their findings of a 3.3–6.2% fat fraction in the pancreas of type 2 diabetic humans [1]. In our paper, we stated that the MRI measurements revealed regions of parenchymal tissue void of any relevant lipid accumulation in all participants, which can be taken as evidence against a uniform pancreatic steatosis. However, the pancreatic fat fraction of type 2 diabetic humans (obtained with the 2-point 3D mDIXONmethod) was up to 4% in some individuals [2]. Thus, it is misleading for Hollingsworth et al to claim that we suggest that there is no fat within the pancreatic parenchymal tissue. The lower pancreas fat fraction reported by us [2] compared Hollingsworth et al [1] is probably due to the noise bias, which does not seem to be corrected for in their method [4]. The third issue raised is that all measurements should have been carried out using a properly established 3-point DIXON technique to remove differences related to spectroscopic and * Michael Roden michael.roden@ddz.uni-duesseldorf.de