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Papers by Stefan Reinsberg

Supplemental Table S1 - Comparison of plasma half-life in mice, active metabolite and partitionin... more Supplemental Table S1 - Comparison of plasma half-life in mice, active metabolite and partitioning of the camptothecin analogues used in this study.

Supplemental FIGS S1 & S2 - Whole tissue section images comparing drug extravasation in H... more Supplemental FIGS S1 & S2 - Whole tissue section images comparing drug extravasation in HCT116 and HT29 xenografts.

Magnetic Resonance in Chemistry, Oct 1, 1999

The cross-polarization dynamics between 1 H and 19 F in a Viton-type fluoroelastomer were studied... more The cross-polarization dynamics between 1 H and 19 F in a Viton-type fluoroelastomer were studied using 19 F magic angle spinning (MAS) and 1 H ! 19 F cross-polarization (CP)/MAS NMR at 188.29 MHz. The phenomenological theory of spin thermodynamics based on the spin temperature hypothesis was employed to describe the polarization transfer between the 1 H and 19 F spin baths. Simultaneous fitting of the evolution of magnetization in the standard CP and a modified CP(TORQUE) experiment, using the exact solutions of the equations for the spin thermodynamics, gave unique sets of the parameters T HF , T H 1 and T F 1 for five separate peaks in the 19 F spectra. The values of T H 1 and T F 1 obtained are consistent with those independently measured by spin-locking experiments. The true values of T HF are significantly larger (by a factor of ca. 4) than those derived from a simple two-parameter fit of the CP behaviour with variable contact time.The temperature dependences of T F 1 and T F 1 were measured between 49 and 86°C. The relationship between the CP dynamics parameters and the local molecular motion in the polymer chains is discussed.

arXiv (Cornell University), May 3, 2017

Introduction: Intra-organ radiation dose sensitivity is becoming increasingly relevant in clinica... more Introduction: Intra-organ radiation dose sensitivity is becoming increasingly relevant in clinical radiotherapy. One method for assessment involves partitioning delineated regions of interest and comparing the relative contributions or importance to clinical outcomes. We show that an intuitive method for dividing organ contours, compound (sub-)segmentation, can unintentionally lead to sub-segments with inconsistent volumes, which will bias sub-segment relative importance assessment. An improved technique, nested segmentation, is introduced and compared. Materials and Methods: Clinical radiotherapy planning parotid contours from 510 patients were segmented. Counts of radiotherapy dose matrix voxels interior to sub-segments were used to determine the equivalency of sub-segment volumes. The distribution of voxel counts within sub-segments were compared using Kolmogorov-Smirnov tests and characterized by their dispersion. Analytical solutions for two-and three-dimensional analogues were derived and sub-segment area/volume were compared directly. Results: Both parotid and 2D/3D region of interest analogue segmentation confirmed compound segmentation intrinsically produces sub-segments with volumes that depend on the region of interest shape and selection location. Significant volume differences were observed when sub-segmenting parotid contours into 18 ths , and vanishingly small sub-segments were observed when sub-segmenting into 96 ths. Central sub-segments were considerably smaller than sub-segments on the periphery. Nested segmentation did not exhibit these shortcomings and produced sub-segments with equivalent volumes when dose grid and contour collinearity was addressed, even when dividing the parotid into 96 ths. Nested segmentation was always faster or equivalent in runtime to compound segmentation. Conclusions: Nested segmentation is more suited than compound segmentation for analyses requiring equal weighting of sub-segments.

Springer eBooks, 2018

Dynamic contrast-enhanced MRI in pre-clinical imaging allows the in-vivo monitoring of vascular, ... more Dynamic contrast-enhanced MRI in pre-clinical imaging allows the in-vivo monitoring of vascular, physiological properties in normal and diseased tissue. There is considerable variation in the methods employed owing to the different questions that can be asked and answered about the physiologic alterations as well as morphologic changes in tissue. Here we review the typical decisions in the design and execution of a dynamic contrast-enhanced MRI study in mice although the findings can easily be transferred to other species. Emphasis is placed on highlighting the many pitfalls that wait for the unaware pre-clinical MRI practitioner and that go often unmentioned in the abundant literature dealing with dynamic contrast-enhanced MRI in animal models.

Physical review, Nov 16, 2016

We present a comment on "Benefits of completing homework for students with different aptitudes in... more We present a comment on "Benefits of completing homework for students with different aptitudes in an introductory electricity and magnetism course", by F. J. Kontur, K. de La Harpe, and N. B. Terry PRST-PER 11, 010105 (2015). Our data show that the conclusions Kontur and coworkers draw from their data may not be generally applicable.

Radiotherapy and Oncology, Oct 1, 2023

Medical Physics, Jun 1, 2013

PURPOSE Fractional anisotropy (FA) from diffusion tensor imaging (DTI) has been suggested as a pr... more PURPOSE Fractional anisotropy (FA) from diffusion tensor imaging (DTI) has been suggested as a predictor of glioma cell density and proliferation activity. The purpose of this study is estimate the glioma cell density inside high-grade glioma radiotherapy target volumes using FA images. METHODS Five patients with histologically-confirmed glioma underwent radiotherapy planning with postoperative magnetic resonance imaging (MRI) and computed tomography. T1 -weighted images with gadolinium contrast enhancement and T2 -weighted fluid attenuated inversion recovery images used for treatment planning were obtained. DTI was obtained using echo planar imaging for 20 noncolinear directions with b=1000 s/mm2 and one additional image with b=0. Diffusion imaging was repeated four times for signal averaging. The gross tumor volume (GTV) was delineated using T1 -weighted and T2 -weighted images. A clinical target volume (CTV) was defined as a 2-cm expansion of the GTV and a shell volume (CTV-shell) between the GTV and CTV contours was created. The distribution of FA inside the GTV, CTV-shell, and normal brain tissue was calculated. Cell density inside the CTV was estimated from FA values using a linear model. RESULTS The mean FA inside the GTV was 0.13±0.08 and inside CTV-shell was 0.20±0.12. The mean FA in normal brain tissue (0.28±0.12) was significantly higher than the mean FA inside the GTV (p=0.003) and CTV-shell (p=0.01). The estimated mean cell density inside CTV-shell was 1.57±0.94 times the mean cell density inside the GTV (p=0.02). CONCLUSION FA values in the GTV and CTV-shell were significantly smaller than values in normal brain regions. FA and estimated cell density values approached those of normal brain tissue as the distance from the GTV increased, consistent with the expectation of a gradual and decreasing presence of tumor cells. Further research is warranted to determine if treatment planning using FA images will improve treatment outcome.

ISMRM Annual Meeting

Clinical prostate carcinoma (PCa) detection with MRI has focused on qualitative assessment. Howev... more Clinical prostate carcinoma (PCa) detection with MRI has focused on qualitative assessment. However, novel Luminal Water Imaging (LWI) provides quantitative information with promising results for detecting PCa. To overcome shortcomings of clinical prostate MRI protocol, we propose using LWI to augment T2-weighted (T2W) images to improve image contrast for PCa detection while maintaining anatomical details needed for radiological diagnosis. Here, we investigate automatic segmentation models and various weighting functions of LWI parameter maps to generate semi-quantitative T2W images that also preserves anatomical detail. Our results show that a combined T2W and LWI parameter image provides enhanced detection of PCa.

Advances in Radiation Oncology

identification of tail vessels. b) Signal phase of mouse tail over the time course of the experim... more identification of tail vessels. b) Signal phase of mouse tail over the time course of the experiment. The vessel of interest is outlined and corresponds with the vessel indicated in a). c) AIF in a mouse tail with a temporal resolution of 100 ms. At this temporal resolution, the shape of the curve is well characterized. Estimation of the Arterial Input Function in a Mouse Tail from the Signal Phase of Projection Profiles Jennifer Moroz, Andrew Yung, Piotr Kozlowski, and Stefan Reinsberg Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada

Contrast Media & Molecular Imaging, 2015

Macromolecular gadolinium (Gd)-based contrast agents are in development as blood pool markers for... more Macromolecular gadolinium (Gd)-based contrast agents are in development as blood pool markers for MRI. HPG-GdF is a 583 kDa hyperbranched polyglycerol doubly tagged with Gd and Alexa 647 nm dye, making it both MR and histologically visible. In this study we examined the location of HPG-GdF in whole-tumor xenograft sections matched to in vivo DCE-MR images of both HPG-GdF and Gadovist. Despite its large size, we have shown that HPG-GdF extravasates from some tumor vessels and accumulates over time, but does not distribute beyond a few cell diameters from vessels. Fractional plasma volume (fPV) and apparent permeability-surface area product (aPS) parameters were derived from the MR concentration-time curves of HPG-GdF. Non-viable necrotic tumor tissue was excluded from the analysis by applying a novel bolus arrival time (BAT) algorithm to all voxels. aPS derived from HPG-GdF was the only MR parameter to identify a difference in vascular function between HCT116 and HT29 colorectal tumors. This study is the first to relate low and high molecular weight contrast agents with matched whole-tumor histological sections. These detailed comparisons identified tumor regions that appear distinct from each other using the HPG-GdF biomarkers related to perfusion and vessel leakiness, while Gadovist-imaged parameter measures in the same regions were unable to detect variation in vascular function. We have established HPG-GdF as a biocompatible multi-modal high molecular weight contrast agent with application for examining vascular function in both MR and histological modalities.

Radiotherapy and Oncology, 2009

Journal of Applied Clinical Medical Physics