Lucy E. Kershaw

Precision in measurements of perfusion and microvascular permeability with T1‐weighted dynamic contrast‐enhanced MRI

Dynamic contrast‐enhanced MRI is used to estimate microvascular parameters by tracer kinetics analysis. The time for the contrast agent to travel from the artery to the tissue of interest (bolus arrival time (BAT)) is an important parameter that must be measured in such studies because inaccurate estimates or neglect of BAT contribute to inaccuracy in model fitting. Furthermore, although the precision with which these parameters are estimated is very important, it is rarely reported. To address these issues, two investigations were undertaken. First, simulated data were used to validate an independent method for estimation of BAT. Second, the adiabatic approximation to the tissue homogeneity model was fitted to experimental data acquired in prostate and muscle tissue of 22 patients with prostate cancer. A bootstrap error analysis was performed to estimate the precision of parameter estimates. The independent method of estimating BAT was found to be more accurate and precise than a model‐fitting approach. Estimated precisions for parameters measured in the prostate gland were 14% for extraction fraction (median coefficient of variation), 19% for blood flow, 28% for permeability‐surface area product, 35% for volume of the extravascular‐extracellular space, and 36% for blood volume. Techniques to further reduce uncertainty are discussed. Magn Reson Med, 2006.

Cellular-interstitial water exchange and its effect on the determination of contrast agent concentration in vivo: Dynamic contrast-enhanced MRI of human internal obturator muscle

The purpose of this study was to assess the effects of cellular‐interstitial water exchange on estimates of tracer kinetics parameters obtained using rapid dynamic contrast‐enhanced (DCE) MRI. Data from the internal obturator muscle of six patients were examined using three models of water exchange: no exchange (NX), fast exchange limit (FXL), and intermediate rate (shutter‐speed [SS]). In combination with additional multiple flip angle (FA) data, a full two‐pool exchange model was also used. The results obtained using the NX model (transfer constant, Ktrans = 0.049 ± 0.027 min–1, apparent interstitial volume, ve = 0.14 ± 0.04) were marginally higher than those obtained using the FXL model (Ktrans = 0.045 ± 0.025 min–1, ve = 0.13 ± 0.04), but the error bars overlapped in two‐thirds of these parameter estimate pairs. Estimates of Ktrans and ve obtained using the SS model exceeded those obtained using the NX model in half the patients, and many estimates, including all those of intracellular residence time of water, ti, were imprecise. Results obtained using the full two‐pool model fell between those obtained using FXL and NX models, and estimates of ti were also imprecise. The results suggest that data obtained using clinically relevant DCE‐MRI are exchange‐insensitive and unsuitable for the assessment of cellular‐interstitial water exchange. Magn Reson Med 60:1011–1019, 2008.

Temporal resolution and SNR requirements for accurate DCE‐MRI data analysis using the AATH model

Dynamic contrast‐enhanced MRI has been used in conjunction with tracer kinetics modeling in a wide range of tissues for treatment monitoring, oncology drug development, and investigation of disease processes. Accurate measurement of model parameters relies on acquiring data with high temporal resolution and low noise, particularly for models with large numbers of free parameters, such as the adiabatic approximation to the tissue homogeneity model for separate measurements of blood flow and vessel permeability. In this simulation study, accuracy of the adiabatic approximation to the tissue homogeneity model was investigated, examining the effects of temporal resolution, noise levels, and error in the measured arterial input function. A temporal resolution of 1.5 s and high SNR (noise sd = 0.05) were found to ensure minimal bias (<5%) in all four model parameters (extraction fraction, blood flow, mean transit time, and extravascular extracellular volume), and the sampling interval can be relaxed to 6 s, if the transit time need not be measured accurately (bias becomes >10%). A 10% error in the measured height of the arterial input function first pass peak resulted in an error of at most 10% in each model parameter. Magn Reson Med, 2010.

Perfusion estimated with rapid dynamic contrast-enhanced magnetic resonance imaging correlates inversely with vascular endothelial growth factor expression and pimonidazole staining in head-and-neck cancer: A pilot study

PURPOSE To analyze, in a pilot study, rapidly acquired dynamic contrast-enhanced (DCE)-MRI data with a general two-compartment exchange tracer kinetic model and correlate parameters obtained with measurements of hypoxia and vascular endothelial growth factor (VEGF) expression in patients with squamous cell carcinoma of the head and neck. METHODS AND MATERIALS Eight patients were scanned before surgery. The DCE-MRI data were acquired with 1.5-s temporal resolution and analyzed using the two-compartment exchange tracer kinetic model to obtain estimates of parameters including perfusion and permeability surface area. Twelve to 16 h before surgery, patients received an intravenous injection of pimonidazole. Samples taken during surgery were used to determine the level of pimonidazole staining using immunohistochemistry and VEGF expression using quantitative real-time polymerase chain reaction. Correlations between the biological and imaging data were examined. RESULTS Of the seven tumors fully analyzed, those that were poorly perfused tended to have high levels of pimonidazole staining (r = -0.79, p = 0.03) and VEGF expression (r = -0.82, p = 0.02). Tumors with low permeability surface area also tended to have high levels of hypoxia (r = -0.75, p = 0.05). Hypoxic tumors also expressed higher levels of VEGF (r = 0.82, p = 0.02). CONCLUSIONS Estimates of perfusion obtained with rapid DCE-MRI data in patients with head-and-neck cancer correlate inversely with pimonidazole staining and VEGF expression.

Benign prostatic hyperplasia: evaluation of T1, T2, and microvascular characteristics with T1-weighted dynamic contrast-enhanced MRI.

To evaluate microvascular and relaxation parameters of prostate and nearby muscle in patients with benign prostatic hyperplasia (BPH), and to examine measurement reproducibility.

Modeling of contrast agent kinetics in the lung using T1-weighted dynamic contrast-enhanced MRI

Assessment of perfusion and capillary permeability is important in both malignant and nonmalignant lung disease. Kinetic modeling of T1‐weighted dynamic contrast‐enhanced MRI (DCE‐MRI) data may provide such an assessment. This study establishes the feasibility and interrelationship of kinetic modeling approaches designed to estimate microvascular properties in malignant and nonmalignant tissues of the lung. DCE‐MRI data were acquired using a low molecular weight contrast agent with 4‐sec temporal resolution in lung cancer patients. A model‐free parameterization and three kinetic models of increasing complexity, each related to the classical Kety model, were applied. Comparison of an extended Kety model and the adiabatic approximation to the tissue homogeneity (AATH) model using Akaikes Information Criterion suggested that in most cases the best description of the lung tumor data is obtained using the AATH model. In the normal lung parenchyma the temporal resolution was insufficient to separate effects of flow and contrast agent leakage and in this case the extended Kety model yielded the best fit to the data. Magn Reson Med, 2009.

A general dual-bolus approach for quantitative DCE-MRI

PURPOSE To present a dual-bolus technique for quantitative dynamic contrast-enhanced MRI (DCE-MRI) and show that it can give an arterial input function (AIF) measurement equivalent to that from a single-bolus protocol. METHODS Five rabbits were imaged using a dual-bolus technique applicable for high-resolution DCE-MRI, incorporating a time resolved imaging of contrast kinetics (TRICKS) sequence for rapid temporal sampling. AIFs were measured from both the low-dose prebolus and the high-dose main bolus in the abdominal aorta. In one animal, TRICKS and fast spoiled gradient echo (FSPGR) acquisitions were compared. RESULTS The scaled prebolus AIF was shown to match the main bolus AIF, with 95% confidence intervals overlapping for fits of gamma-variate functions to the first pass and linear fits to the washout phase, with the exception of one case. The AIFs measured using TRICKS and FSPGR were shown to be equivalent in one animal. CONCLUSION The proposed technique can capture even the rapid circulation kinetics in the rabbit aorta, and the scaled prebolus AIF is equivalent to the AIF from a high-dose injection. This allows separate measurements of the AIF and tissue uptake curves, meaning that each curve can then be acquired using a protocol tailored to its specific requirements.

MRI-guided prostate adaptive radiotherapy - A systematic review.

Dose escalated radiotherapy improves outcomes for men with prostate cancer. A plateau for benefit from dose escalation using EBRT may not have been reached for some patients with higher risk disease. The use of increasingly conformal techniques, such as step and shoot IMRT or more recently VMAT, has allowed treatment intensification to be achieved whilst minimising associated increases in toxicity to surrounding normal structures. To support further safe dose escalation, the uncertainties in the treatment target position will need be minimised using optimal planning and image-guided radiotherapy (IGRT). In particular the increasing usage of profoundly hypo-fractionated stereotactic therapy is predicated on the ability to confidently direct treatment precisely to the intended target for the duration of each treatment. This article reviews published studies on the influences of varies types of motion on daily prostate position and how these may be mitigated to improve IGRT in future. In particular the role that MRI has played in the generation of data is discussed and the potential role of the MR-Linac in next-generation IGRT is discussed.

Late tissue effects following radiotherapy and neoadjuvant hormone therapy of the prostate measured with quantitative magnetic resonance imaging.

BACKGROUND AND PURPOSE To use quantitative MRI to detect changes in the vascular and MR relaxation characteristics of the prostate gland 1 year after external beam radiotherapy. MATERIALS AND METHODS Twenty-one patients underwent MRI before and after external beam radiotherapy for prostatic adenocarcinoma. Tracer kinetics analysis was applied to data from regions of interest in prostate tumour, normal prostate peripheral zone and muscle to obtain estimates of blood flow, extravascular-extracellular volume, blood volume and capillary permeability surface area product. T(1) and T(2) were also measured in these regions. RESULTS Significant changes (p<0.05) after radiotherapy were found in all three tissues examined. Tumour blood flow was 0.34 and 0.14 ml (ml tissue)(-1) min(-1) before and after treatment, respectively, and T(1) increased from 922 to 1,070 ms. In normal peripheral zone, extravascular-extracellular volume increased from 0.21 to 0.52 ml (ml tissue)(-1), and T(2) decreased from 126 to 106 ms. In muscle, both permeability surface area product and T(2) rose, from 0.02 to 0.06 ml (ml tissue)(-1) min(-1) and from 50 to 56 ms, respectively. CONCLUSIONS Quantitative MRI can be used to measure significant changes in both vascular and MR relaxation properties of the prostate and nearby muscle following treatment for prostate cancer using external beam radiotherapy.

Dynamic contrast-enhanced MRI in patients with muscle-invasive transitional cell carcinoma of the bladder can distinguish between residual tumour and post-chemotherapy effect

INTRODUCTION Treatment of muscle-invasive bladder cancer with chemotherapy results in haemorrhagic inflammation, mimicking residual tumour on conventional MR images and making interpretation difficult. The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to estimate descriptive and tracer kinetic parameters post-neoadjuvant chemotherapy and to investigate whether parameters differed in areas of residual tumour and chemotherapy-induced haemorrhagic inflammation (treatment effect, Tr-Eff). METHODS AND MATERIALS Twenty-one patients underwent DCE-MRI scans with 2.5s temporal resolution before and following neoadjuvant chemotherapy. Regions-of-interest (ROIs) were defined in areas suspicious of residual tumour on T2-weighted MRI scans. Data were analysed semi-quantitatively and with a two-compartment exchange model to obtain parameters including relative signal intensity (rSI80s) and plasma perfusion (Fp) respectively. The bladder was subsequently examined histologically after cystectomy for evidence of residual tumour and/or Tr-Eff. Differences in parameters measured in areas of residual tumour and Tr-Eff were examined using Students t-test. RESULTS Twenty-four abnormal sites were defined after neoadjuvant chemotherapy. On pathology, 10 and 14 areas were identified as residual tumour and Tr-Eff respectively. Median rSI80s and Fp were significantly higher in areas of residual tumour than Tr-Eff (rSI80s = 2.9 vs 1.7, p < 0.001; Fp = 20.7 vs 9.1 ml/100ml/min, p = 0.03). The sensitivity and specificity for differentiating residual tumour from Tr-Eff were 70% and 100% (rSI80s), 60% and 86% (Fp), and 75% and 100% when combined. CONCLUSION DCE-MRI parameters obtained post-treatment are capable of distinguishing between residual tumour and treatment effect in patients treated for bladder cancer with neoadjuvant chemotherapy.