T2-weighted morphological MR-images of representative HS type 1, HS type 2 and no-HS hippocampi.

<p>Image resolutions are 43x43x300 μm, respectively. The PCL is significantly narrower in HS type 1 and HS type 2 in comparison to no-HS hippocampi (two-sided arrows). With respect to CA1, the narrowing affects the whole sector in HS type 1 specimens, while it is limited to the upper half of CA1 in direction to CA2 in HS type 2 (triangles). The dentate gyrus (DG) is broadened and focally not discernible in HS type 1 and HS type 2, whereas it can be identified as a distinct thin black line (arrow) in no-HS specimens.</p

Illustration of the quantitative MR-parameters product and area, including color-coded maps of T2*-time of HS type 1, HS type 2 and no-HS hippocampi.

<p>The parameter product, as is exemplarily shown in the upper row, is derived by multiplying widths a and b of the PCL and can be illustrated as a rectangle. The parameter area (second row) refers to the area of the PCL, which is skirted by the segmentation mask, shown in yellow. T2*-time is determined as mean value within the segmentation mask, defining the area of the PCL.</p

T2-weighted morphological MR-images of representative HS type 1, HS type 2 and no-HS hippocampi.

<p>Image resolutions are 43x43x300 μm, respectively. The PCL is significantly narrower in HS type 1 and HS type 2 in comparison to no-HS hippocampi (two-sided arrows). With respect to CA1, the narrowing affects the whole sector in HS type 1 specimens, while it is limited to the upper half of CA1 in direction to CA2 in HS type 2 (triangles). The dentate gyrus (DG) is broadened and focally not discernible in HS type 1 and HS type 2, whereas it can be identified as a distinct thin black line (arrow) in no-HS specimens.</p

Boxplots of the parameters product, area and T2*-time for HS type 1, HS type 2 and no-HS hippocampi.

<p>Boxplots of the parameters product, area and T2*-time for HS type 1, HS type 2 and no-HS hippocampi.</p

Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology

<div><p>Purpose</p><p>Adamantinomatous craniopharyngiomas (ACP) as benign sellar brain tumors are challenging to treat. In order to develop robust <i>in vivo</i> drug testing methodology, the murine orthotopic craniopharyngioma model (PDX) was characterized by magnetic resonance imaging (MRI) and histology in xenografts from three patients (ACP1-3).</p><p>Methods</p><p>In ACP PDX, multiparametric MRI was conducted to assess morphologic characteristics such as contrast-enhancing tumor volume (CETV) as well as functional parameters from dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) including area-under-the-curve (AUC), peak enhancement (PE), time-to-peak (TTP) and apparent diffusion coefficient (ADC). These MRI parameters evaluated in 27 ACP PDX were correlated to histological features and percentage of vital tumor cell content.</p><p>Results</p><p>Qualitative analysis of MRI and histology from PDX revealed a similar phenotype as seen in patients, although the MRI appearance in mice resulted in a more solid tumor growth than in humans. CETV were significantly higher in ACP2 xenografts relative to ACP1 and ACP3 which correspond to respective average vitality of 41%, <10% and 26% determined histologically. Importantly, CETV prove tumor growth of ACP2 PDX as it significantly increases in longitudinal follow-up of 110 days. Furthermore, xenografts from ACP2 revealed a significantly higher AUC, PE and TTP in comparison to ACP3, and significantly increased ADC relative to ACP1 and ACP3 respectively. Overall, DCE-MRI and DWI can be used to distinguish vital from non-vital grafts, when using a cut off value of 15% for vital tumor cell content.</p><p>Conclusions</p><p>MRI enables the assessment of craniopharyngioma PDX vitality <i>in vivo</i> as validated histologically.</p></div

Patient-specific origin of xenografts and study results.

<p>Patient-specific origin of xenografts and study results.</p

Comparison of primary human MRI and histology with the induced model.

<p>MR images and corresponding histology of an ACP patient (ACP2) showing the primary tumor and relapse after 145 days are illustrated in comparison with an example of a direct vital descendent of the surgically removed primary tumor specimen implanted into the nude mouse number one out of ten (ACP2 M1). T2 weighted images show a cystic component within the craniopharyngioma in the human patient (a and b; arrow) with contrast enhancement in the rim of the lesion (e and f; arrow) at baseline (a and e) as compared to 145 days later (b and f) with an increase in size over time. The craniopharyngioma xenograft in the mouse is inhomogeneous in T2 (c and d) and post contrast T1 (g and h) weighted images. The T2w hyperintense and T1 contrast enhancing areas in the tumor increase over 110 days as well (c and d; g and h). Histology of the primary tumor (i) shows similar characteristics to the descendent tumors in human (j) and in mice (k and k`) in terms of vital tumor proportions (arrow), wet keratin (asterisk) and calcification (arrowhead). Vital tumor areas (arrow, k´) in the murine graft were also identified on MRI (arrows, d and h) by T2 hyperintensity and contrast enhancing areas in T1. However, calcified regions appear hypointense (arrowhead, k´, d and h). PDX tumor volume (n = 5) defined 28 and 138 days post transplantation (dpt) in T2 weighted as well as post contrast T1 weighted images revealed a significant increase over time (p<0.05) (l).</p

Comparison of patient specific engrafted tumors.

<p>Primary (a, e and i) and descended transplanted ACP tissue (b, c, f, g, j and k) show comparable histological appearance with regressive changes e.g. wet keratin (*) and calcifications (arrowhead) with estimated vitality indicated in the magnified images. Associated T1 weighted MR images after contrast medium application (d, h and l) are shown for comparison with histological appearance.</p

MRI data correlated with patient specific grafts and vitality.

<p>a: Patient derived engrafted tumors were analyzed in terms of T2 tumor volume (T2 TV), contrast-enhancing tumor volume (CETV), apparent diffusion coefficient (ADC), area-under-the-curve (AUC), peak enhancement (PE) and time-to-peak (TTP). b: Corresponding data were also evaluated in matters of vitality with a cutoff of 15% discriminating non-vital from vital engrafted tumors. Significant differences are marked by an asterisk (*). Detailed results e.g. mean values and p-values are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0197895#pone.0197895.s002" target="_blank">S2 Table</a>.</p