Analysis of left ventricle regional myocardial motion for cardiac radioablation: Left ventricular motion analysis.

PURPOSE: Left ventricle (LV) regional myocardial displacement due to cardiac motion was assessed using cardiovascular magnetic resonance (CMR) cine images to establish region-specific margins for cardiac radioablation treatments. METHODS: CMR breath-hold cine images and LV myocardial tissue contour points were analyzed for 200 subjects, including controls (n = 50) and heart failure (HF) patients with preserved ejection fraction (HFpEF, n = 50), mid-range ejection fraction (HFmrEF, n = 50), and reduced ejection fraction (HFrEF, n = 50). Contour points were divided into segments according to the 17-segment model. For each patient, contour point displacements were determined for the long-axis (all 17 segments) and short-axis (segments 1-12) directions. Mean overall, tangential (longitudinal or circumferential), and normal (radial) displacements were calculated for the 17 segments and for each segment level. RESULTS: The greatest overall motion was observed in the control group-long axis: 4.5 ± 1.2 mm (segment 13 [apical anterior] epicardium) to 13.8 ± 3.0 mm (segment 6 [basal anterolateral] endocardium), short axis: 4.3 ± 0.8 mm (segment 9 [mid inferoseptal] epicardium) to 11.5 ± 2.3 mm (segment 1 [basal anterior] endocardium). HF patients exhibited lesser motion, with the smallest overall displacements observed in the HFrEF group-long axis: 4.3 ± 1.7 mm (segment 13 [apical anterior] epicardium) to 10.6 ± 3.4 mm (segment 6 [basal anterolateral] endocardium), short axis: 3.9 ± 1.3 mm (segment 8 [mid anteroseptal] epicardium) to 7.4 ± 2.8 mm (segment 1 [basal anterior] endocardium). CONCLUSIONS: This analysis provides an estimate of epicardial and endocardial displacement for the 17 segments of the LV for patients with normal and impaired LV function. This reference data can be used to establish treatment planning margin guidelines for cardiac radioablation. Smaller margins may be used for patients with higher degree of impaired heart function, depending on the LV segment.

Commissioning a four-dimensional Computed Tomography Simulator for minimum target size due to motion in the Anterior-Posterior direction: a procedure and treatment planning recommendations.

The purpose of this work is to develop a procedure for commissioning four-dimensional computed tomography (4DCT) algorithms for minimum target reconstruction size, to quantify the effect of anterior-posterior (AP) motion artifacts on known object reconstruction for periodic and irregular breathing patterns, and to provide treatment planning recommendations for target sizes below a minimum threshold. A mechanical platform enabled AP motion of a rod and lung phantom during 4DCT acquisition. Static, artifact-free scans of the phantoms were first acquired. AP sinusoidal and patient breathing motion was applied to obtain 4DCT images. 4DCT reconstruction artifacts were assessed by measuring the apparent width and angle of the rod. Comparison of known tumor diameters and volumes between the static image parameters with the 4DCT image sets was used to quantify the extent of AP reconstruction artifact and contour deformation. Examination of the rod width, under sinusoidal motion, found it was best represented during the inhale and exhale phases for all periods and ranges of motion. From the gradient phases, the apparent width of the rod decreased with increasing amplitude and decreasing period. The rod angle appeared larger on the reconstructed images due to the presence of motion artifact. The apparent diameters of the spherical tumors on the gradient phases were larger/equivalent than the true values in the AP/LR direction, respectively, while the exhale phase consistently displayed the spheres at the approximately correct diameter. The Eclipse calculated diameter matched closely with the true diameter on the exhale phase and was found to be larger on the inhale, MIP, and Avg scans. The procedure detailed here may be used during the acceptance and commissioning period of a computed tomography simulator or retroactively when implementing a SBRT program to determine the minimum target size that can be reliably reconstructed.

Fast and sensitive dynamic oxygen-enhanced MRI with a cycling gas challenge and independent component analysis.

PURPOSE: There is a critical need for non-invasive imaging biomarkers of tumor oxygenation to assist in patient stratification and development of hypoxia targeting therapies. Using a cycling gas challenge and independent component analysis (ICA), we sought to improve the sensitivity and speed of existing oxygen enhanced MRI (OE-MRI) techniques to detect changes in oxygenation with dynamically acquired T1 W signal intensity images (dOE-MRI). METHODS: Mice were implanted with SCCVII, HCT-116, BT-474, or SKOV3 tumors in the dorsal subcutaneous region and imaged at 7T. T1 W images were acquired during a respiratory challenge with alternating 2-minute periods of air and 100% oxygen for three cycles. Data were analyzed with ICA and oxygenation maps were generated and compared to corresponding histology sections stained for hypoxia (pimonidazole) and blood vessels (CD31). RESULTS: Cycling air-oxygen-air gas challenges were well tolerated and ICA permitted extraction of the oxygen-enhancing component in all imaged tumors from four different models. Comparison with synthetic response functions showed that dOE-MRI does not require any a-priori knowledge of the physiological response. The fraction of O2 -negative dOE-MRI voxels that correlate inversely with the ICA gas-cycling component correspond well with the histological hypoxic fraction in SCCVII tumors (r = 0.91, p = 0.0016) but did not correlate in HCT-116 tumors (r = 0.13, p = 0.81). CONCLUSIONS: Using ICA and adding a cycling gas challenge extends the sensitivity of OE-MRI and allows the oxygenation status of tumors to be assessed in as little as six minutes. These findings support further development of OE-MRI as a biomarker of tumor oxygenation.

Dynamic contrast-enhanced MRI in mice: an investigation of model parameter uncertainties.

PURPOSE: To establish the experimental factors that dominate the uncertainty of hemodynamic parameters in commonly used pharmacokinetic models. METHODS: By fitting simulation results from a multiregion tissue exchange model (Multiple path, Multiple tracer, Indicator Dilution, 4 region), the precision and accuracy of hemodynamic parameters in dynamic contrast-enhanced MRI with four tracer kinetic models is investigated. The impact of various injection rates as well as imprecise knowledge of the arterial input functions is examined. RESULTS: Fast injections are beneficial for K(trans) precision within the extended Tofts model and within the two-compartment exchange model but do not affect the other models under investigation. Biases from errors in the arterial input functions are mostly consistent in size and direction for the simple and the extended Tofts model, while they are hardly predictable for the other models. Errors in the hematocrit introduce the greatest loss in parameter accuracy, amounting to an average K(trans) bias of 40% for a 30% overestimation throughout all models. CONCLUSION: This simulation study allows the detailed inspection of the isolated impact from various experimental conditions on parameter uncertainty. Because parameter uncertainty comparable to human studies was found, this study represents a validation of preclinical dynamic contrast-enhanced MRI for modeling human tumor physiology.

Rapid measurement of arterial input function in mouse tail from projection phases.

PURPOSE: To measure the arterial input function (AIF) in a mouse tail at high temporal resolution with signal phase of MR projections. METHODS: The technique involves the acquisition of one 2D image before injection, followed by a series of projections before, during, and after contrast injection. Differences in the signal phase, relative to the mean preinjection phase, were calculated and converted into a concentration of Gd. RESULTS: An AIF with a temporal resolution of 100 ms was measured and verified with colorimetry (in a flow phantom) and mass spectrometry analysis (in vivo). The projection-based AIF is expected to better represent the rapid contrast kinetics in the blood following injection, thus improving the accuracy of quantitative dynamic contrast-enhanced-MRI analysis. Colorimetry experiments confirmed that signal phase is preferred over magnitude for a precise determination of an AIF. In-vivo experiments demonstrate the feasibility of our approach in mice. CONCLUSION: AIFs can be measured quickly and precisely using phase from projections. Phase data are sensitive to the flow velocity; but this sensitivity is significantly reduced when flow compensation was used.

Radiosensitizing oxygenation changes in murine tumors treated with VEGF-ablation therapy are measurable using oxygen enhanced-MRI (OE-MRI).

PURPOSE: There is a significant need for a widely available, translatable, sensitive and non-invasive imaging biomarker for tumor hypoxia in radiation oncology. Treatment-induced changes in tumor tissue oxygenation can alter the sensitivity of cancer tissues to radiation, but the relative difficulty in monitoring the tumor microenvironment results in scarce clinical and research data. Oxygen-Enhanced MRI (OE-MRI) uses inhaled oxygen as a contrast agent to measure tissue oxygenation. Here we investigate the utility of dOE-MRI, a previously validated imaging approach employing a cycling gas challenge and independent component analysis (ICA), to detect VEGF-ablation treatment-induced changes in tumor oxygenation that result in radiosensitization. METHODS: Murine squamous cell carcinoma (SCCVII) tumor-bearing mice were treated with 5 mg/kg anti-VEGF murine antibody B20 (B20-4.1.1, Genentech) 2-7 days prior to radiation treatment, tissue collection or MR imaging using a 7 T scanner. dOE-MRI scans were acquired for a total of three repeated cycles of air (2 min) and 100% oxygen (2 min) with responding voxels indicating tissue oxygenation. DCE-MRI scans were acquired using a high molecular weight (MW) contrast agent (Gd-DOTA based hyperbranched polygylcerol; HPG-GdF, 500 kDa) to obtain fractional plasma volume (fPV) and apparent permeability-surface area product (aPS) parameters derived from the MR concentration-time curves. Changes to the tumor microenvironment were evaluated histologically, with cryosections stained and imaged for hypoxia, DNA damage, vasculature and perfusion. Radiosensitizing effects of B20-mediated increases in oxygenation were evaluated by clonogenic survival assays and by staining for DNA damage marker γH2AX. RESULTS: Tumors from mice treated with B20 exhibit changes to their vasculature that are consistent with a vascular normalization response, and result in a temporary period of reduced hypoxia. DCE-MRI using injectable contrast agent HPG-GDF measured decreased vessel permeability in treated tumors, while dOE-MRI using inhaled oxygen as a contrast agent showed greater tissue oxygenation. These treatment-induced changes to the tumor microenvironment result in significantly increased radiation sensitivity, illustrating the utility of dOE-MRI as a non-invasive biomarker of treatment response and tumor sensitivity during cancer interventions. CONCLUSIONS: VEGF-ablation therapy-mediated changes to tumor vascular function measurable using DCE-MRI techniques may be monitored using the less invasive approach of dOE-MRI, an effective biomarker of tissue oxygenation that can monitor treatment response and predict radiation sensitivity.

Hyperbranched polyglycerols as trimodal imaging agents: design, biocompatibility, and tumor uptake.

Combining various imaging modalities often leads to complementary information and synergistic advantages. A trimodal long-circulating imaging agent tagged with radioactive, magnetic resonance, and fluorescence markers is able to combine the high sensitivity of SPECT with the high resolution of MRI over hours and days. The fluorescence marker helps to confirm the in vivo imaging information at the microscopic level, in the context of the tumor microenvironment. To make a trimodal long-circulating probe, high-molecular-weight hyperbranched polyglycerols (HPG) were modified with a suitable ligand for (111)In radiolabeling and Gd coordination, and additionally tagged with a fluorescent dye. The resulting radiopharmaceutical and contrast agent was nontoxic and hemocompatible. Measured radioactively, its total tumor uptake increased from 2.6% at 24 h to 7.3% at 72 h, which is twice the increase expected due to tumor growth in this time period. Both in vivo MRI and subsequent histological analyses of the same tumors confirmed maximum HPG accumulation at 3 days post injection. Furthermore, Gd-derivatized HPG has an excellent contrast enhancement on T1-weighted MRI at 10× lower molar concentrations than commercially available Galbumin. HPG derivatized with gadolinium, radioactivity, and fluorescence are thus long-circulating macromolecules with great potential for imaging of healthy and leaky blood vessels using overlapping multimodal approaches and for the passive targeting of tumors.

Device for sectioning prostatectomy specimens to facilitate comparison between histology and in vivo MRI.

PURPOSE: To develop a device for sectioning prostatectomy specimens that would facilitate comparison between histology and in vivo MRI. MATERIALS AND METHODS: A multi-bladed cutting device was developed, which consists of an adjustable box capable of accommodating a prostatectomy specimen up to 85 mm in size in the lateral direction, a "plunger" tool to press on the excised gland from the top to prevent it from rolling or sliding during sectioning, and a multi-bladed knife assembly capable of holding up to 21 blades at 4-mm intervals. The device was tested on a formalin fixed piece of meat and subsequently used to section a prostatectomy specimen. Histology sections were compared with T2-weighted MR images acquired in vivo before the prostatectomy procedure. RESULTS: The prostatectomy specimen slices were very uniform in thickness with each face parallel to the other with no visible sawing marks on the sections by the blades after the cut. MRI and histology comparison showed good correspondence between the two images. CONCLUSION: The developed device allows sectioning of prostatectomy specimens into parallel cuts at a specific orientation and fixed intervals. Such a device is useful in facilitating accurate correlation between histology and MRI data.

Technical Note: Cardiac synchronized volumetric modulated arc therapy for stereotactic arrhythmia radioablation - Proof of principle.

PURPOSE: Ventricular tachycardia (VT) is a rapid, abnormal heart rhythm that can lead to sudden cardiac death. Current treatment options include antiarrhythmic drug therapy and catheter ablation, both of which have only modest efficacy and have potential complications. Cardiac radiosurgery has the potential to be a noninvasive and efficient treatment option for VT. Cardiac motion, however, must be accounted for to ensure accurate dose delivery to the target region. Cardiac synchronized volumetric modulated arc therapy (CSVMAT) aims to minimize the dose delivered to normal tissues by synchronizing beam delivery with a cardiac signal, irradiating only during the quiescent intervals of the cardiac cycle (when heart motion is minimal) and adjusting the beam delivery speed in response to heart rate changes. METHODS: A CSVMAT plan was adapted from a conventional VMAT plan and delivered on a Varian TrueBeam linear accelerator. The original VMAT plan was divided into three interleaved CSVMAT phases, each consisting of alternating beam-on and beam-off segments synchronized to a sample heart rate. Trajectory log files were collected for the original VMAT and CSVMAT deliveries and the dose distributions were measured with Gafchromic EBT-XD film. RESULTS: Analysis of the trajectory log files showed successful synchronization with the sample cardiac signal. Film analysis comparing the original VMAT and CSVMAT dose distributions returned a gamma passing rate of 99.14% (2%/2 mm tolerance). CONCLUSIONS: The film results indicated excellent agreement between the dose distributions of the original and cardiac synchronized beam deliveries. This study demonstrates a proof of principle cardiac synchronization strategy for precise radiation treatment plan delivery and adjustment to a variable heart rate. The cardiac synchronized technique may be advantageous in radioablation for VT.

Automated air kerma strength quality assurance of permanent seed implant prostate brachytherapy sources using vendor autoradiographs.

PURPOSE: To develop a novel quality assurance (QA) program to determine the air kerma strength (AKS) of brachytherapy seeds within preloaded needles using autoradiographs alone, without jeopardizing sterility or necessitating procedural changes either by the vendor or in the operating room. METHODS AND MATERIALS: Digital autoradiographs of QA seed orders and sterile preloaded needles were acquired. Regions of interest of each preloaded seed were determined through an iterative scanning process identifying changes from background levels to radioactivity exposure. Average exposure values through the center of each region of interest were fitted with a Gaussian curve and Full Width at Half Maximums (FWHMs) were calculated. The two-dimensional exposure-scaled FWHM (Exp2D) measurements for the QA seed orders were plotted against measured AKS values and related using a linear curve fit that was adjusted using the third-party assay average AKS and applied as a calibration curve to convert Exp2D to AKS. RESULTS: Estimated seed AKS was found to have a strong dependence on position within the holding tray because of imager positioning inconsistencies. Calculated seed AKS for patient-specific seed orders using the curve scaling factor varied from the nominal order AKS by 1.1 ± 0.9% and from the third-party assay measurements by 0.0 ± 0.4%. CONCLUSIONS: This work depicts a clinically useful tool to aid in QA of preloaded brachytherapy permanent seed implant needles without compromising sterility or increasing clinical workloads. With this procedure, each individual seed's AKS can be verified automatically before a patient's scheduled implant or retroactively when auditing patient records.

Dose-painted volumetric modulated arc therapy of high-grade glioma using 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine positron emission tomography.

OBJECTIVE: To determine whether dose painting with volumetric modulated arc therapy for high-grade gliomas using 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (18F-FDOPA) positron emission tomography (PET) could achieve dose-escalated coverage of biological target volumes (BTVs) without increasing the dose to cranial organs at risk (OARs). METHODS: 10 patients with high-grade gliomas underwent CT, MRI, and 18F-FDOPA PET/CT images for post-operative radiation therapy planning. Two volumetric modulated arc therapy plans were retrospectively generated for each patient: a conventional plan with 60 Gy in 30 fractions to the planning target volume delineated on MRI and a dose-escalated plan with a maximum dose of 80 Gy in 30 fractions to BTVs. BTVs were created by thresholding 18F-FDOPA PET/CT uptake using a linear quadratic model that assumed tracer uptake was linearly related to tumour cell density. The maximum doses and equivalent uniform doses of OARs were compared. RESULTS: The median volume of the planning target volume receiving at least 95% of the prescribed dose (V 95%) was 99.6% with and 99.5% without dose painting. The median V 95% was >99.2% for BTVs. The maximum doses and equivalent uniform doses to the OARs did not differ significantly between the conventional and dose-painted plans. CONCLUSION: Using commercially available treatment planning software, dose painting for high-grade gliomas was feasible with good BTV coverage and no significant change in the dose to OARs. ADVANCES IN KNOWLEDGE: A novel treatment planning strategy was used to achieve dose painting for gliomas with BTVs obtained from 18F-FDOPA PET/CT using a radiobiological model.

Dynamic Contrast-Enhanced MRI.

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.

Heterogeneous distribution of trastuzumab in HER2-positive xenografts and metastases: role of the tumor microenvironment.

Most HER2-positive metastatic breast cancer patients continue to relapse. Incomplete access to all target HER2-positive cells in metastases and tumor tissues is a potential mechanism of resistance to trastuzumab. The location of locally bound trastuzumab was evaluated in HER2-positive tissues in vivo and as in vivo xenografts or metastases models in mice. Microenvironmental elements of tumors were related to bound trastuzumab using immunohistochemical staining and include tight junctions, vasculature, vascular maturity, vessel patency, hypoxia and HER2 to look for correlations. Trastuzumab was evaluated alone and in combination with bevacizumab. Dynamic contrast-enhanced magnetic resonance imaging parameters of overall vascular function, perfusion and apparent permeability were compared with matched histological images of trastuzumab distribution and vascular patency. Trastuzumab distribution is highly heterogeneous in all models examined, including avascular micrometastases of the brain and lung. Trastuzumab distributes well through the extravascular compartment even in conditions of high HER2 expression and poor convective flow in vivo. Microregional patterns of trastuzumab distribution in vivo do not consistently correlate with vascular density, patency, function or maturity; areas of poor trastuzumab access are not necessarily those with poor vascular supply. The number of vessels with perivascular trastuzumab increases with time and higher doses and dramatically decreases when pre-treated with bevacizumab. Areas of HER2-positive tissue without bound trastuzumab persist in all conditions. These data directly demonstrate tissue- and vessel-level barriers to trastuzumab distribution in vivo that can effectively limit access of the drug to target cells in brain metastases and elsewhere.

Combined use of diffusion-weighted MRI and 1H MR spectroscopy to increase accuracy in prostate cancer detection.

OBJECTIVE: The objective of our study was to establish the sensitivity and specificity for prostate cancer detection using a combined 1H MR spectroscopy and diffusion-weighted MRI approach. SUBJECTS AND METHODS: Forty-two men (mean age +/- SD, 69.3 +/- 4.7 years) with prostate cancer were studied using endorectal T2-weighted imaging, 2D chemical shift imaging (CSI), and isotropic apparent diffusion coefficient (ADC) maps. Regions of interest (ROIs) were drawn around the entire gland, central gland, and peripheral zone tumor, diagnostically defined as low signal intensity on T2-weighted images within a sextant that was biopsy-positive for tumor. Lack of susceptibility artifact on a gradient-echo B0 map through the slice selected for CSI and no high signal intensity on external array T1-weighted images confirmed the absence of significant hemorrhage after biopsy. CSI voxels were classified as nonmalignant or as tumor (ROI included > or = 30% or > or = 70% tumor). Choline-citrate (Cho/Cit) ratios and average ADCs were calculated for every voxel. A plot of Cho/Cit ratios versus ADCs yielded a line of best separation of tumor voxels from nonmalignant voxels. Receiver operating characteristic (ROC) curves were plotted for Cho/Cit ratios alone, ADCs alone, and a combination of the two. RESULTS: The Cho/Cit ratios were significantly higher (p < 0.001) and the ADCs were significantly lower (p < 0.006) in tumor-containing voxels than in non-tumor-containing voxels. When voxels containing 30% or more tumor were considered positive, the area under the ROC curves using combined MR spectroscopy and ADC (0.81) was similar to that of Cho/Cit alone (0.79) and better than ADC alone (0.66). When voxels containing 70% or more tumor were considered positive and cutoffs to achieve a 90%-or-greater sensitivity chosen, a combination of Cho/Cit and ADC achieved a significant improvement in specificity compared with Cho/Cit alone (p < 0.0001) or ADC alone (p < 0.0001). CONCLUSION: When voxels containing > or = 70% tumor are considered positive, the combined use of MR spectroscopy and diffusion-weighted MRI increases the specificity for prostate cancer detection while retaining the sensitivity compared with MR spectroscopy alone or diffusion-weighted MRI alone.

Interhemispheric Difference Images from Postoperative Diffusion Tensor Imaging of Gliomas.

Introduction Determining the full extent of gliomas during radiotherapy planning can be challenging with conventional T1 and T2 magnetic resonance imaging (MRI). The purpose of this study was to develop a method to automatically calculate differences in the fractional anisotropy (FA) and mean diffusivity (MD) values in target volumes obtained with diffusion tensor imaging (DTI) by comparing with values from anatomically homologous voxels on the contralateral side of the brain. Methods Seven patients with a histologically confirmed glioma underwent postoperative radiotherapy planning with 1.5 T MRI and computed tomography. DTI was acquired using echo planar imaging for 20 noncolinear directions with b = 1000 s/mm2 and one additional image with b = 0, repeated four times for signal averaging. The distribution of FA and MD was calculated in the gross tumor volume (GTV), shells 0-5 mm, 5-10 mm, 10-15 mm, 15-20 mm, and 20-25 mm outside the GTV, and the GTV mirrored in the left-right direction (mirGTV). All images were aligned to a template image, and FA and MD interhemispheric difference images were calculated. The difference in mean FA and MD between the regions of interest was statistically tested using two-sided paired t-tests with α = 0.05. Results The mean FA in mirGTV was 0.20 ± 0.04, which was larger than the FA in the GTV (0.12 ± 0.03) and shells 0-5 mm (0.15 ± 0.03) and 5-10 mm (0.17 ± 0.03) outside the GTV. The mean MD (×10-3 mm2/s) in mirGTV was 0.93 ± 0.09, which was smaller than the MD in the GTV (1.48 ± 0.19) and the peritumoral shells. The distribution of FA and MD interhemispheric differences followed the same trends as FA and MD values. Conclusions This study successfully implemented a method for calculation of FA and MD differences by comparison of voxel values with anatomically homologous voxels on the contralateral side of the brain. Further research is warranted to determine if radiotherapy planning using these images can be used to improve target delineation.

Multi-modal magnetic resonance imaging and histology of vascular function in xenografts using macromolecular contrast agent hyperbranched polyglycerol (HPG-GdF).

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.

A complete distortion correction for MR images: I. Gradient warp correction.

MR images are known to be distorted because of both gradient nonlinearity and imperfections in the B0 field, the latter caused either by an imperfect shim or sample-induced distortions. This paper describes in detail a method for correcting the gradient warp distortion, based on a direct field mapping using a custom-built phantom with three orthogonal grids of fluid-filled rods. The key advance of the current work over previous contributions is the large volume of the mapping phantom and the large distortions (>25 mm) corrected, making the method suitable for use with large field of view, extra-cranial images. Experimental measurements on the Siemens AS25 gradient set, as installed on a Siemens Vision scanner, are compared with a theoretical description of the gradient set, based on the manufacturer's spherical harmonic coefficients. It was found that over a volume of 320x200x340 mm3 distortions can be successfully mapped to within the voxel resolution of the raw imaging data, whilst outside this volume, correction is still good but some systematic errors are present. The phenomenon of through-plane distortion (also known as 'slice warp') is examined in detail, and the perturbation it causes to the measurements is quantified and corrected. At the very edges of the region of support provided by the phantom, through-plane distortion is extreme and only partially corrected by the present method. Solutions to this problem are discussed. Both phantom and patient data demonstrate the efficacy of the gradient warp correction.

A complete distortion correction for MR images: II. Rectification of static-field inhomogeneities by similarity-based profile mapping.

Radiotherapy treatment planning relies on the use of geometrically correct images. This paper presents a fully automatic tool for correcting MR images for the effects of B(0) inhomogeneities. The post-processing method is based on the gradient-reversal technique of Chang and Fitzpatrick (1992 IEEE Trans. Med. Imaging 11 319-29) which combines two identical images acquired with a forward- and a reversed read gradient. This paper demonstrates how maximization of mutual information for registration of forward and reverse read gradient images allows the elimination of user interaction for the correction. Image quality is preserved to a degree not reported previously.