Effect of Fat: Assessment of Apparent Diffusion Coefficient

fix of Fat Assessment of App arent Diffusion CoefficientAbstractObjectives Recent studies guide indicated that excessive plump down whitethorn confound sound judgment of public exposure in organs with senior high school lucub yard content, such as the liver and breast. However, the conclusion of this picture in the kidney, which is non considered a major adipose tissue repository site, form unclear. This survey tested the hypothesis that renal luscious may impact DWI parameters, and proposes a three-compartment model (TCM) to circumvent this effect.Methods Using computer simulations, we investigated the effect of fat on assessment of apparent dispersion coefficient (ADC), intravoxel unconnected-motion (IVIM) and TCM-derived pure-diffusivity. In domestic help pigs fed a high-cholesterol ( obese) or normal fodder (Lean) (n=7 each), DWI parameters were metrical employ IVIM and correlated to renal histology. IVIM-derived pure diffusivity was also compared among 15 necessity hypertension (EH) patients classified by BMI (high vs. normal). Fin aloney, pure diffusivity was mensural and compared in 8 patients with atherosclerotic renal artery stenosis (ARAS) and 5 lusty subjects development IVIM and TCM.Results Simulations showed that unaccounted fat results in the underestimation of intravoxel incoherent-motion (IVIM)-derived pure-diffusivity, particularly at lower fat contents. Moreoer, TCM, which incorporates highly diffusion-weighted images (b2500s/mm2), could correct for fat-dependent underestimation. Animal studies confirmed lower ADC and pure-diffusivity in Obese vs. Lean pigs with otherwise healthy kidneys. Similarly, EH patients with high BMI had lower ADC (1.9 vs. 2.110-3 mm2/s) and pure-diffusivity (1.7 vs. 1.910-3mm2/s) than those with normal BMI. Pure-diffusivity work out victimisation IVIM was not different between the ARAS and healthy subjects, but TCM revealed importantly lower diffusivity in ARAS.Conclusions Excessive renal fat may typeface underestimation of renal ADC and pure-diffusivity, which may hinder detection of renal pathology. Models account for fat contribution may help reduce the variability of diffusivity metrical using DWI.Keywords Renal adiposity, Diffusion-weighted mental imagery, intravoxel incoherent motion, fleshiness. Over the past two decades, diffusion-weighted imaging (DWI) has evolved to an important tool for working neurological disorders (1-3), while application of this method acting for characterization of abdominal pathological conditions awaited improved hardware and square-built pulse sequences all over virtually a decade (4). In the kidney, DWI has been use to investigate chronic kidney disease (CKD) (5), renal lesions (6), and deteriorating allografts (7). Nevertheless, the contribution of tubular work and hemodynamics to the apparent diffusion constant (ADC), the diffusion quantitative business leader of the single(a) compartment mono-exponential model, compl icates tissue characterization and renal DWI analysis (8). This encouraged implementation of models incorporating a larger number of compartments to differentiate pure diffusion from pseudo-diffusive components. Indeed, in the kidney the intra-voxel incoherent motion (IVIM) analytical method, which utilizes a two-compartment model associated with pure diffusion and flow, showed transcendence over the mono-exponential decay model (9, 10).However, recent studies on hepatic DWI de preconditionine fat as a potential third compartment with a substantive confounding effect (11, 12), even in non-steatotic livers (13, 14) or other organs (15). Abdominal DWI is typically performed using an echo-planar imaging (EPI) readout, which uses a piss-only excitation. Selected excitation or fat suppression methods prevent contribution of the fat prognostic associated with peaks spectrally contrasted from water, but micklenot effectively eliminate the mark from fat components with resonance fr equencies culture to water proton frequency. For instance, peaks between 4.2-5.3 ppm associated with triglycerides, which account for nearly 8.7% of the total in vivo fat content, remain unsuppressed (11). Moreover, in the kidney, which is located in the vicinity of bowel, competency artifacts may significantly reduce the efficacy of spectral fat suppression. Because the diffusion constant of lipid molecules is orders of magnitude smaller than that in water and remains nearly unattenuated over the conventional bleed of b- determine, the amplitude of the fat sign of the zodiac, specially at high b- take accounts, can be prominent compared to the attenuated water augury (16), and therefore has a considerable impact on DWI parameters assessment (17).The epidemic of obesity stresses the importance of characterization of the effect of ectopic fat on DWI parameters, particularly in subjects with high body mass index (BMI). Increased renal adiposity (18, 19) may potentially interfere with recitation of DWI in the kidney in obese subjects, but to date this effect has not been evaluated. The aim of this regard was to explore the effect of renal fat assemblage and suboptimal suppression on DWI parameters. We investigated this effect using computer simulations and verified the flaw in a large animal model of obesity, and in healthy subjects and in the presence of renal pathological conditions in humans. We hypothesized that residual MR signal from fat causes underestimation of renal ADC and IVIM pure-diffusivity, the magnitude of which may approximate a reduction in these parameters elicited by renal pathology. Moreover, we suggest that the fat-dependency of DWI parameters may be corrected by estimating the MR signal of excessive fat using heavily diffusion-weighted images.Assuming that an unattenuated fat signal acts as an nonsymbiotic compartment, we suppose our model by adding a third exponential decay term to the bi-exponential IVIM model to account for t he contribution of fat(1)In our notation, C and are the fractions of extravascular water and fat in the DWI signal intensity. D solid, Dslow, andDfat are diffusion coefficients for extravascular water (pure-diffusivity), intravascular flow-dependent component (pseudo-diffusion), and fat, respectively. The product of the fat diffusion coefficient and the b-values, over the conventional range of b-values is small such that the exponential part of the third term can be approximated by one. This simplifies the last term in Equation (1) to a constant signal offset as follows(2)Considering that at higher b-values ( kibibyte s/mm2) conventionally used in DWI, the water-component of the signal intensity decays to nearly a few percent of its value at b0 (b=0 s/mm2), while the fat-related fraction (FRF), f, remains nearly unattenuated over the imaging b-value spectrum, the magnitude of FRF and its impact on calculated DWI parameters becomes significant.I. SimulationsSimulations in this study pursued cardinal aims. First, to show that in the absence of fat signal, the three-compartment model (TCM) reduces to IVIM. This would essentially moderate that a non-zero FRF is not merely a result of overfitting the data of an per se two-compartment system into a three-compartment model, and in fact represents a third independent compartment. Second, to investigate the influence of FRF, as illustrated in equation (1), on the diffusion parameters calculated using the bi-exponential IVIM model. Third, to examine the effect of signal-to-noise ratio (SNR) on the accuracy of DWI parameters assessed using IVIM and TCM, particularly since increasing the degrees of freedom in TCM per se reduces the stability of the regularization methods. Finally, to test if in the presence of fat signal the DWI parameters calculated using IVIM and TCM would be b-value dependent.We simulated the total MR signal using the TCM, including fast and slow decays associated with intra- and extravascular flui d, as well as the FRF signal as a third compartment. Simulations were performed for diffusion parameters similar to DWI values reported for the kidney (10), over a range of FRFs (0-10%) and SNRs (2.5-50dB) (Table 1). IVIM and TCM were used to extract DWI parameters. In TCM, the total MR signal intensity for all b-values was subtracted by the signal intensity from the interchangeable voxel of the high b-value (2500 s/mm2) image, and the data were then fitted to a bi-exponential model. Table 1 shows the values used in the simulations.To verify the b-value dependency, DWI parameters were calculated from a set of b-values with the highest value being either 600, 1000, or 2000 s/mm2.II. Animal study both animal procedures followed the Guideline for the Care and practise of research lab Animals ( internal Research Council, National Academy Press, Washington, DC, 1996) and were approved by the Institutional Animal Care and Use Committee at mayonnaise Clinic.Fourteen domestic swine in th is study were fed ad lib for 16 weeks. Seven animals consumed a normal victuals (Controls) and the other half (Obese) a high fat/carbohydrate diet (5B4L Purina Test Diet, Richmond, IN) containing (in % kcal) 17% protein, 20% complex carbohydrates, 20% fructose, and 43% fat and supplemented with 2% cholesterol and 0.7% sodium cholate. We have recently shown that this diet induces obesity and adiposity (20).Diffusion-weighted MRI scans were performed at the completion of diet. Renal garishness and hemodynamics were assessed 2-3 geezerhood apart from MR scans, using multi-detector computed tomography (MDCT). Prior to each in vivo study animals were anesthetized (Telazol 5mg/kg and xylazine 2mg/kg in saline), and anesthesia maintained with intravenous ketamine hydrochloride (0.2 mg/kg/min) and xylazine (0.03 mg/kg/min) (for CT), or inhaled 1-2% isoflurane (for MRI) throughout the strain of imaging. Blood pressure was measured using an arterial catheter during the MDCT scanning sessi on.Animals were blasted with 10cc of heparin and euthanized with a lethal intravenous dose of sodium pentobarbital (100 mg/kg) a few days after the in vivo studies. Then the kidneys were remove and immersed in saline containing heparin. The tissue was stored at -80C or preserve in formalin for histology.a. Diffusion-weighted Imaging (DWI)DWI was performed on a 3T scanner (GE checkup Systems, Milwaukee, Wisconsin) using a torso array coil. Images were collected using a single-shot echo-planar sequence with bipolar gradient. In all animals, 4-6 coronal slices in cater-cornered planes were collected for b-values 50, 100, 200, 300, 600, 800 and 1000 s/mm2. MR parameters were set to TR/TE 1800/79ms, field of side 35cm, Bandwidth 648Hz/pixel, Number of averages 3, slice thickness 2.5mm, and matrix size 128128. All acquisitions were performed during hang up respiration.b. MDCT imagingRenal hemodynamics were assessed from contrast-enhanced MDCT images, as previously detailed (21). A pigtail catheter was mod through the left jugular vein to the superior vena cava to inject contrast media during the scan. Then animals were moved to MDCT unit (Somatom Sensation 64 randomness medical examination Solutions, Forchheim, Germany). Following localization of the kidneys, a bolus of iopamidol (0.5 ml/kg over 2s) was injected, and after a 3-second delay, 140 consecutive scans were acquired over approximately 3 minutes. After the flow scan and an additional contrast injection, a volume study was performed. Axial images were acquired at helical acquisition with thickness of 0.6mm and resolving power of 512512, and reconstructed at 5mm thickness.c. lipide PanelLipid (total cholesterol, triglyceride, high absorption lipid (HDL)) was measured (Roche) at the Mayo Immunochemical Core Laboratory from kind samples, and low-density lipid (LDL) was calculated.d. Morphological StudiesImages were acquired using an ApoTome microscope (Carl ZEISS SMT, Oberkochen, Germany). Renal fi brosis was quantified by colorimetric measurements in 5m slides stained for trichrome. Tubular dilation was measured in Periodic acid-Schiff (PAS)-stained slides counterstained with Hemotoxylin. Intracellular lipid accumulation was assessed by colorimetric measurements in Oil-Red-O stained slides from frozen tissue counterstained with Hematoxylin.III. Human studyThe study was approved by the Institutional Review Board of the Mayo Clinic, in accordance with the Declaration of Helsinki and the Health Insurance Portability and office Act (HIPAA) guidelines. All patients provided written informed consent ahead enrollment. xv patients with essential hypertension (EH) were recruited from an on-going study, to study the effect of renal fat on DWI parameters. Patients were divided in two free radicals based on their BMI an obese group (n=10, BMI30kg/m2) and a lean group (n=5, BMI 20-25kg/m2). Additionally, diffusion parameters assessments in healthy vs. impair (post-stenotic) kidneys, with and without fat correction, were compared in eight patients with atherosclerotic renal artery stenosis (ARAS), and five healthy controls.a. DWIIn patients 3-8 axial images were acquired on 3T scanner (GE Medical Systems, Milwaukee, WI and Siemens Medical Systems, Erlangen, Germany) with MR parameters TR/TE, Bandwidth, Slice thickness, matrix size, and b-values were set to 2000-2400/60-94ms, 1953 Hz/pixel, 7mm, 128128 or 160160, and 100, 300, 600, 900 (s/mm2) in the first study with EH patients. In ARAS and Control subjects the TR/TE were 2600-4286/59-112ms. Pure-diffusivity was calculated from b-values 300 s/mm2 and fat-related fraction was assessed from high b-values, 2000-2500 s/mm2.b. Clinical parameters and Lipid PanelClinical and laboratory parameters including age, sex, weight, BMI, blood pressure, serum creatinine, estimated glomerular filtration rate (eGFR), and lipid panel levels were evaluated at study entry by measuring stick procedures.IV. Data analysisa. DWIPixel- by-pixel maps of quantitative indices of mono-exponential model, ADC, and bi- and tri-exponential models, IVIM and TCM parameters, respectively, were generated (Figure 1), as shown previously (22). The threshold for fast vs. slow components was set to 300s/mm2 in both animal and patient studies (23). wide cortical regions of interest (ROIs) were drawn on b0 DWI images and transferred to the maps as detailed before (22). Mean values of ADC and IVIM parameters were calculated by averaging values in all corresponding ROIs for all slices in the subject.b. MDCTUsing contrast-enhanced MDCT in animals, single-kidney volume, GFR, perfusion, and renal blood flow (RBF) were calculated. To calculate renal function and hemodynamics, the cortical and medullary signal attenuation vs. time curves were fitted to an extended -variate model. Regional blood volumes and mean shipping times were calculated to estimate cortical and medullary perfusion and blood flows (products of perfusion and the corre sponding volumes). Total RBF was assessed as the sum of cortical and medullary flows. Finally, GFR was evaluated using the monger of the cortical proximal tubular curve, as previously shown (21).Data compendium softwareAll analyses were performed in MATLAB (MathWork, Natick, MA, USA) and Analyze (Biomedical Imaging Resource, Mayo Clinic, MN, USA).V. statistical AnalysisSimulation results are shown as mean STD, and in vivo results as Median First Quartile Third Quartile. Minimum sample size was calculated using power analysis for minimum power value of 0.8. Non-parametric Mann-Whitney was used for semblance among groups. For p values