Repeatability of arterial input functions and kinetic parameters in muscle obtained by dynamic contrast enhanced MR imaging of the head and neck

BACKGROUND: Quantification of pharmacokinetic parameters in dynamic contrast enhanced (DCE) MRI is heavily dependent on the arterial input function (AIF). In the present patient study on advanced stage head and neck squamous cell carcinoma (HNSCC) we have acquired DCE-MR images before and during chemo radiotherapy. We determined the repeatability of image-derived AIFs and of the obtained kinetic parameters in muscle and compared the repeatability of muscle kinetic parameters obtained with image-derived AIF's versus a population-based AIF. MATERIALS AND METHODS: We compared image-derived AIFs obtained from the internal carotid, external carotid and vertebral arteries. Pharmacokinetic parameters (ve, Ktrans, kep) in muscle-located outside the radiation area-were obtained using the Tofts model with the image-derived AIFs and a population averaged AIF. Parameter values and repeatability were compared. Repeatability was calculated with the pre- and post-treatment data with the assumption of no DCE-MRI measurable biological changes between the scans. RESULTS: Several parameters describing magnitude and shape of the image-derived AIFs from the different arteries in the head and neck were significantly different. Use of image-derived AIFs led to higher pharmacokinetic parameters compared to use of a population averaged AIF. Median muscle pharmacokinetic parameters values obtained with AIFs in external carotids, internal carotids, vertebral arteries and with a population averaged AIF were respectively: ve (0.65, 0.74, 0.58, 0.32), Ktrans (0.30, 0.21, 0.13, 0.06), kep (0.41, 0.32, 0.24, 0.18). Repeatability of pharmacokinetic parameters was highest when a population averaged AIF was used; however, this repeatability was not significantly different from image-derived AIFs. CONCLUSION: Image-derived AIFs in the neck region showed significant variations in the AIFs obtained from different arteries, and did not improve repeatability of the resulting pharmacokinetic parameters compared with the use of a population averaged AIF. Therefore, use of a population averaged AIF seems to be preferable for pharmacokinetic analysis using DCE-MRI in the head and neck area

Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

<p>Abstract</p> <p>Background</p> <p>High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors.</p> <p>Methods</p> <p>Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 10⁵U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BED_tumor= 30.6 Gy).</p> <p>Results</p> <p>In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals.</p> <p>Conclusion</p> <p>The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.</p

Simulating the effect of input errors on the accuracy of Tofts' pharmacokinetic model parameters

Pharmacokinetic modeling in Dynamic Contrast Enhanced (DCE)-MRI is an elegant and useful method that provides valuable insight into angiogenesis in cancer and inflammatory diseases. Despite its widespread use, the reliability of the model results is still questioned, as many factors hamper the calculation of the model's parameters, resulting in the poor reproducibility and accuracy of the method. Pharmacokinetic modeling relies on the knowledge of inputs such as the Arterial Input Function (AIF) and of the tissue contrast agent concentration, both of which are difficult to accurately measure. Any errors in the measurement of either of the inputs propagate into the calculated pharmacokinetic model parameters (PMPs), and the significance of the effect depends on the source of the measurement error. In this work we systematically investigate the effect of the incorrect estimation of the parameters describing the inputs of the model on the calculated PMPs when using Tofts' model. Furthermore, we analyze the dependence of these errors on the native values of the PMPs. We show that errors on the measurement of the native T1 as well as errors on the parameters describing the initial peak of the AIF have the largest impact on the calculated PMPs. The parameter whose error has the least effect is the one describing the slow decay of the AIF. The effect of input parameter (IP) errors on the calculated PMPs is found to be dependent on the native set of PMPs: this is particularly true for the errors in the flip angle, and for the errors in parameters describing the initial AIF peak. Conversely the effect of T1 and AIF scaling errors on the calculated PMPs is only slightly dependent on the native PMP

Reproducibility of the gadolinium concentration measurements and of the fitting parameters of the vascular input function in the superior sagittal sinus in a patient population

It is widely recognised that the measurement of the arterial input function (AIF) is a key issue and a major source of errors in the pharmacokinetic modelling of dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI) data, and the modality of the AIF determination is still a matter of debate. In this study we addressed the problem of the intrinsic variability of the AIF within the imaged volume of a DCE-MRI scan by systematically investigating the change in the concentration of contrast agent over time and the fit parameters of the derived vascular input function (VIF) obtained from the superior sagittal sinus (SSS) of a patient population that was scanned longitudinally during treatment for high grade glioma. From a total of 82 scanning sessions, we compared the results obtained with three different DCE-MRI protocols and between two different fitting functions. We applied a correction algorithm to the measured concentration-time curves to minimize the effect of the low temporal resolution on the VIF, and investigated the effect of this algorithm on the reproducibility. Finally, where possible, we compared the signal obtained in the SSS to the signal obtained in the middle cerebral artery. We found a good intrapatient reproducibility of both the measured gadolinium concentrations and VIF parameters, and that the variation of the parameters due to slice location within a patient was significantly lower than the intra patient variation. Intrapatient, interscan differences were significantly less marked than inter-patient differences showing a good intraclass correlation coefficient. We did encounter a MRI protocol dependence of the VIF fitting parameters. The correction algorithm significantly improved the reproducibility of the fitting parameters. These results support the idea that the use of a patient specific measured AIF, not necessarily averaged over a large volume, offers a significant benefit with respect to an external AIF or a measured cohort average AIF. (C) 2010 Elsevier Inc. All rights reserve

MRI in Crohn's disease

Technological developments have extended the role of MRI in the evaluation of the gastrointestinal tract. The potential of MRI to evaluate disease activity in Crohn's disease has been investigated extensively, as MRI has intrinsic advantages over other techniques, including noninvasiveness and the absence of ionizing radiation. For perianal fistulizing disease MRI has become a mainstay in evaluation of disease. as localization and extent of disease can be very well appreciated using both T2-weighted and T1-weighted sequences, fat suppression, and intravenous contrast medium. Imaging of the small bowel and colon in Crohn's disease is more complicated due to bowel peristalsis and respiratory movement. However, using fast breathhold sequences and intravenous spasmolytic medication, images of good diagnostic quality can be acquired. To obtain sufficiently distended bowel, which in our estimation is a prerequisite for evaluation of the bowel, MR enteroclysis can be performed. However, applicability of different oral contrast media has been studied, as a noninvasive method for bowel distension would be preferable. Abdominal MRI is a valuable imaging technique for evaluation of luminal, transmural. and extraintestinal manifestations of Crohn's disease as degree of disease activity, presence of luminal pathology (e.g.. stenoses). and extraintestinal manifestations of disease (e.g.. abscesses, fistulas) can be accurately assesse

Reproducibility of functional MR imaging results using two different MR systems

BACKGROUND AND PURPOSE: In the application of functional MR imaging for presurgical planning, high reproducibility is required. We investigated whether the reproducibility of functional MR imaging results in healthy volunteers depended on the MR system used. METHODS: Visual functional MR imaging reproducibility experiments were performed with 12 subjects, by using two comparable 1.5-T MR systems from different manufacturers. Each session consisted of two runs, and each subject underwent three sessions, two on one system and one on the other. Reproducibility measures D (distance in millimeters) and R(size) and R(overlap) (ratios) were calculated under three conditions: same session, which compared runs from one session; intersession, which compared runs from different sessions but from the same system; and intermachine, which compared runs from the two different systems. The data were averaged per condition and per system, and were compared. RESULTS: The average same-session values of the reproducibility measures did not differ significantly between the two systems. The average intersession values did not differ significantly as to the volume of activation (R(size)), but did differ significantly as to the location of this volume (D and R(overlap)). The average intermachine reproducibility did not differ significantly from the average intersession reproducibility of the MR system with the worst reproducibility. CONCLUSION: The location of activated voxels from visual functional MR imaging experiments varied more between sessions on one MR system than on other MR system. The amount of the activated voxels is independent of the MR system used. We suggest that sites performing functional MR imaging for presurgical planning measure the intersession reproducibility to determine an accurate surgical safety margi

Perianal Crohn Disease: Evaluation of Dynamic Contrast-enhanced MR Imaging as an Indicator of Disease Activity

Purpose: To prospectively determine clinical value of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the evaluation of disease activity in perianal Crohn disease (CD). Materials and Methods: Patients provided written informed consent. Study approval was waived by an institutional review board. Thirty-three patients with perianal CD underwent pelvic MR imaging; 17 were male (mean age, 37.4 years +/- 10.8 [standard deviation]; age range, 18-54 years) and 16 were female (mean age, 32.0 years +/- 8.3; age range, 16-43 years). Dynamic contrast-enhanced MR imaging was performed; time-intensity curves (TICs) were obtained. Each pixel was classified as one of six predefined TIC shape types. For each MR imaging examination, a region of interest (ROI) was drawn around the fistula on the single section corresponding to the most extensive and most hyperintense lesion; maximum enhancement (ME), slope of enhancement, and TIC shapes were calculated. Absolute and relative numbers of pixels for each curve type were calculated in a two-dimensional ROI. These results were compared with Perianal Disease Activity Index (PDAI),C-reactive protein (CRP) level, an MR imaging-based severity score, and clinical outcome. A Spearman rank correlation test was used to calculate correlation coefficients between dynamic contrast-enhanced MR imaging parameters and reference parameters. A Mann-Whitney U test was used to calculate differences in dynamic contrast-enhanced MR imaging parameters between predefined groups of patients. Results: Significant correlations were found between the absolute amounts of the TIC shape types and PDAI and between ROI volume and PDAI. The ratio of quickly enhancing versus slowly enhancing pixels correlated with higher MR imaging scores as did the ROI volume. The absolute amounts of pixels displaying TIC types 2, 3, 4, and 5 correlated significantly with MR imaging score. CRP level showed a significant correlation with mean ME. Larger numbers of quickly enhancing pixels were observed in patients who needed medication changes or developed new abscesses during follow-up. Conclusion: Dynamic contrast-enhanced MR imaging can help determine disease activity in perianal CD and might be helpful in selecting a subpopulation of patients who should be monitored more closely for development of more extensive diseas