Patients with colorectal cancer are frequently presented with liver metastases for which (partial) resection is often the best therapy. However, the future remnant liver, the remaining part of the liver after resection, should allow adequate liver function to avoid liver failure. This thesis presents novel methods for the accurate voxel-wise estimation of the future remnant liver’s function based on pharmacokinetic modeling of dynamic contractenhanced (DCE)MRI. The methods comprise a variety of novel techniques for DCE-MRI of the liver: 1) 4D registration of the DCE series; 2) delineation of the liver, the liver vasculature and the liver’s anatomical segments; 3) pharmacokinetic (PK) modeling of the perfusion based on the intra-cellular contrast agent Gd-EOB-DTPA (Primovist); 4) assessment of the relation between DCE-MRI and hepatobiliary scintigraphy (HBS). Spatial alignment of the voxels in the 4D DCE-MRI is an important requirement for PK modeling. We exploit the proximity of deformation fields to sequentially register images in an ordered fashion. The global liver displacement helps in predicting the deformation ‘tendency’ along the time axis. The deformation tendency allows us to obtain a better starting point for the registration. Such a method aims to start the registration optimization close to the optimum and avoid getting trapped in a local minimum. We apply a liver-specific contrast agent, due to which the liver shows @en

Purpose Pharmacokinetic models facilitate assessment of properties of the micro-vascularization based on DCE-MRI data. However, accurate pharmacokinetic modeling in the liver is challenging since it has two vascular inputs and it is subject to large deformation and displacement due to respiration. Methods We propose an improved pharmacokinetic model for the liver that (1) analytically models the arrival-time of the contrast agent for both inputs separately; (2) implicitly compensates for signal fluctuations that can be modeled by varying applied flip-angle e.g. due to B1-inhomogeneity. Orton’s AIF model is used to analytically represent the vascular input functions. The inputs are independently embedded into the Sourbron model. B1-inhomogeneity-driven variations of flip-angles are accounted for to justify the voxel’s displacement with respect to a pre-contrast image. Results The new model was shown to yield lower root mean square error (RMSE) after fitting the model to all but a minority of voxels compared to Sourbron’s approach. Furthermore, it outperformed this existing model in the majority of voxels according to three model-selection criteria. Conclusion Our work primarily targeted to improve pharmacokinetic modeling for DCE-MRI of the liver. However, other types of pharmacokinetic models may also benefit from our approaches, since the techniques are generally applicable.

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Objectives: To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with ^99m Tc-mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. Methods: Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using ^99m Tc-mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. Results: A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p < 0.001 respectively). There was a strong agreement between the functional share determined with both modalities (ICC = 0.944, 95% CI 0.863–0.978, n = 20). There was a significant negative correlation between liver aminotransferases and bilirubin for both MUR and Ki. Conclusions: Assessment of liver function with DHCE-MRI is comparable with that of ^99m Tc-mebrofenin HBS and has the potential to be combined with diagnostic MRI imaging. This can therefore provide a one-stop-shop modality for the preoperative assessment of patients undergoing liver surgery. Key Points: • Quantitative assessment of liver function using hepatobiliary scintigraphy is performed in the preoperative assessment of patients undergoing liver surgery in order to prevent posthepatectomy liver failure. • Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) is an emerging method to quantify liver function and can serve as a potential alternative to hepatobiliary scintigraphy. • Assessment of liver function with dynamic gadoxetate-enhanced MRI is comparable with that of hepatobiliary scintigraphy and has the potential to be combined with diagnostic MRI imaging.

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The Couinaud classification of hepatic anatomy partitions the liver into eight functionally independent segments. Detection and segmentation of the hepatic vein (HV), portal vein (PV) and inferior vena cava (IVC) plays an important role in the subsequent delineation of the liver segments. To facilitate pharmacokinetic modeling of the liver based on the same data, a 4D DCE-MR scan protocol was selected. This yields images with high temporal resolution but low spatial resolution. Since the liver's vasculature consists of many tiny branches, segmentation of these images is challenging. The proposed framework starts with registration of the 4D DCE-MRI series followed by region growing from manually annotated seeds in the main branches of key blood vessels in the liver. It calculates the Pearson correlation between the time intensity curves (TICs) of a seed and all voxels. A maximum correlation map for each vessel is obtained by combining the correlation maps for all branches of the same vessel through a maximum selection per voxel. The maximum correlation map is incorporated in a level set scheme to individually delineate the main vessels. Subsequently, the eight liver segments are segmented based on three vertical intersecting planes fit through the three skeleton branches of HV and IVC's center of mass as well as a horizontal plane fit through the skeleton of PV. Our segmentation regarding delineation of the vessels is more accurate than the results of two state-of-the-art techniques on five subjects in terms of the average symmetric surface distance (ASSD) and modified Hausdorff distance (MHD). Furthermore, the proposed liver partitioning achieves large overlap with manual reference segmentations (expressed in Dice Coefficient) in all but a small minority of segments (mean values between 87% and 94% for segments 2-8). The lower mean overlap for segment 1 (72%) is due to the limited spatial resolution of our DCE-MR scan protocol.

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In Dynamic Contrast-Enhanced MRI (DCE-MRI) of the liver, a series of images is acquired over a period of 20 minutes. Due to the patient's breathing, the liver is subject to a substantial displacement between acquisitions. Furthermore, due to its location in the abdomen, the liver also undergoes marked deformation. The large deformations combined with variation in image contrast make accurate liver registration challenging. We present a registration framework that incorporates a liver segmentation to improve the registration accuracy. The segmented liver serves as region-of-interest to our in-house developed registration method called ALOST (autocorrelation of local image structure). ALOST is a continuous optimization method that uses local phase features to overcome space-variant intensity distortions. The proposed framework can confine the solution field to the liver and allow for ALOST to obtain a more accurate solution. For the segmentation part, we use a level-set method to delineate the liver in a so-called contrast enhancement map. This map is obtained by computing the difference between the last and registered first volume from the DCE series. Subsequently, we slightly dilate the segmentation, and apply it as the mask to the other DCE-MRI volumes during registration. It is shown that the registration result becomes more accurate compared with the original ALOST approach.

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