Extended Kety Model Research Articles

Dynamic contrast-enhanced magnetic resonance imaging may act as a biomarker for vascular damage in normal appearing brain tissue after radiotherapy in patients with glioblastoma.

BackgroundDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising perfusion method and may be useful in evaluating radiation-induced changes in normal-appearing brain tissue.PurposeTo assess whether radiotherapy induces changes in vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) derived from DCE-MRI in normal-appearing brain tissue and possible relationships to radiation dose given.Material and MethodsSeventeen patients with glioblastoma treated with radiotherapy and chemotherapy were included; five were excluded because of inconsistencies in the radiotherapy protocol or early drop-out. DCE-MRI, contrast-enhanced three-dimensional (3D) T1-weighted (T1W) images and T2-weighted fluid attenuated inversion recovery (T2-FLAIR) images were acquired before and on average 3.3, 30.6, 101.6, and 185.7 days after radiotherapy. Pre-radiotherapy CE T1W and T2-FLAIR images were segmented into white and gray matter, excluding all non-healthy tissue. Ktrans and Ve were calculated using the extended Kety model with the Parker population-based arterial input function. Six radiation dose regions were created for each tissue type, based on each patient’s computed tomography-based dose plan. Mean Ktrans and Ve were calculated over each dose region and tissue type.ResultsGlobal Ktrans and Ve demonstrated mostly non-significant changes with mean values higher for post-radiotherapy examinations in both gray and white matter compared to pre-radiotherapy. No relationship to radiation dose was found.ConclusionAdditional studies are needed to validate if Ktrans and Ve derived from DCE-MRI may act as potential biomarkers for acute and early-delayed radiation-induced vascular damages. No dose-response relationship was found.

017 Combined heart lung MRI protocol for simultaneous interrogation of heart and lung structure

Introduction Many conditions considered to be primary lung diseases are independently associated with adverse cardiovascular outcome. Systemic inflammation and subsequent fibrosis are hypothesised mechanisms. However, beyond the mechanical impact on right heart, characterisation of myocardial involvement in lung disease remains limited. We present a combined heart-lung MRI protocol which allows simultaneous interrogation of heart and lung structure and function. Methods Protocol (1.5T Siemens Avanto) includes steady state free precession (SSFP) cine imaging of the heart (standard long and short axis views), followed by inspiration and expiration cine lung imaging (sagittal planes). T2 prepared SFFP and T1 MOLLIE images are acquired in standard cardiac planes and left and right lungs. Dynamic contrast enhanced MRI (DCE-MRI) sequences are performed using free breathing 2D saturation-recovery FLASH dynamic acquisitions in four planes (two LV short axis slices, left and right lung sagittal slices) with temporal resolution equal to 50% of patient’s heart rate. Three boluses of gadolinium contrast (dotarem) are administered: 0.005 mmol/kg, followed by 2 min of dynamic acquisitions; 0.05 mmol/kg followed by 6 min of dynamics; final dose of 0.1 mmol/kg. Finally, late enhancement imaging and post-contrast T1 mapping are performed. Overall each scan protocol lasted for approximately 60 min. Results Parametric mapping and LGE imaging provides direct tissue characterisation. Myocardial and lung contrast agent kinetics are modelled from the DCE images in matlab (Extended Kety Model) to determine heart and lung capillary permeability (Ktrans), extracellular volume (ECV) and plasma volume fraction (vp). Regions of interest are drawn in the LV and RV cavities to obtain arterial input functions (AIF). The low dose AIF is multiplied by a factor of ten and the first pass peak is combined with the high dose AIF curve in order to correct for saturation effects (Figure 1). Examples of ECV maps are shown in Figure 2 and 3. Conclusions This combined heart lung protocol is an efficient and comprehensive imaging tool for simultaneous myocardial and pulmonary assessment. It has a potential to help elucidate complex links between pulmonary and myocardial pathologies, and is a model for other dual organ parametric MR imaging.

Correlation of quantitative dynamic contrast-enhanced MRI with microvascular density in necrotic, partial necrotic, and viable liver tumors in a rabbit model.

The purpose of this study was to examine the correlation of quantitative dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) with microvessel density (MVD) in necrotic, partial necrotic, and viable tumors using a rabbit VX2 liver tumor model. Nine rabbits were used for this study. The complete necrotic area (CNA), partial necrotic area (PNA), and viable tumor area (VTA) of liver tumors were experimentally induced by radiofrequency ablation (RFA). DCE‐MRI data were processed based on the extended Kety model to estimate Ktrans,ve and vp parameters. The boundaries among CNA, PNA, and VTA were delineated based on H&E stain images, and MVD was assessed for each subregion of each VX2 tumor based. There were no correlations between ph‐parameters (Ktrans,ve, and vp) and MVD for CNA. For PNA, the Ktrans values were positively correlated with the MVD (r=0.8124,p<0.0001). For VTA, we found a positive correlation between Ktrans values and the MVD (r=0.5743,p<0.05). Measuring from both the PNA and the VTA, mean Ktrans values were positively correlated with mean MVD (r=0.8470,p<0.0001). In a rabbit VX2 liver tumor model, Ktrans values correlated well with MVD counts of PNA and VTA in liver tumors.PACS number(s): 87.19.If MRI

A prospective translational study investigating molecular predictors of resistance and response to regorafenib (REG) monotherapy in RAS mutant (mt) metastatic colorectal cancer (mCRC): Initial magnetic resonance imaging (MRI) sub-study result.

580 Background: REG that has single agent efficacy in patients (pts) with refractory mCRC, is known to have anti-angiogenic activities. The benefit of REG in unselected pts is modest. Thus, the identification of predictive biomarkers is critical for treatment stratification. PROSPECT-R study aims to identify genetic and radiological mechanisms of primary and acquired REG resistance in RAS mt mCRC patients. Methods: Multiparametric MRI studies including dynamic contrast enhancement (DCE)-MRI and diffusion weighted imaging (DWI) were acquired pre- and at day 15 post-treatment on a 1.5T Siemens Avanto MR scanner. Regions of interest of the entire chosen target metastatic lesion were drawn by a senior radiologist and the following imaging parameters were generated: volume transfer constant (Ktrans) derived from a pharmacokinetic analysis based on the extended Kety model and apparent diffusion coefficient (ADC) calculated using a mono-exponential fitting algorithm; median values of ADC and Ktrans were reported. Results: The first seven enrolled pts were analysed; a single target lesion per patient was chosen (5 liver and 2 pelvic metastases). At day 15 post treatment, a marked decrease (68-81%) of median tumour Ktrans was observed in 4 out of 7 pts; the remaining 3 patients showed no significant median Ktrans change (-36 to + 17%). Overall, the cohort average Ktrans decreased from 0.17 to 0.07 min-1(58%). No significant ADC changes were observed at day 15. Of the 4 pts with Ktrans reduction on day 15, 1 achieved RECIST 1.1 partial response (38% reduction in target lesions), 2 had stable disease and 1 progressed, based on CT assessments performed at 8 weeks of REG therapy; 3/7 pts with no Ktrans change progressed within 2 months of initiating REG. When modified Choi criteria were applied, 3/4 pts with Ktrans reduction were classified as responders. Conclusions: REG may have early anti-angiogenic affects; DCE-MRI could be a potential predicting biomarker in pts treated with REG. Further analysis within PROSPECT-R may elucidate genetic biomarkers to validate these findings. Clinical trial information: EUDRACT No: 2014- 003579-51.

A quantitative MRI method for imaging blood-brain barrier leakage in experimental traumatic brain injury.

Blood-brain barrier (BBB) disruption is common following traumatic brain injury (TBI). Dynamic contrast enhanced (DCE) MRI can longitudinally measure the transport coefficient Ktrans which reflects BBB permeability. Ktrans measurements however are not widely used in TBI research because it is generally considered to be noisy and possesses low spatial resolution. We improved spatiotemporal resolution and signal sensitivity of Ktrans MRI in rats by using a high-sensitivity surface transceiver coil. To overcome the signal drop off profile of the surface coil, a pre-scan module was used to map the flip angle (B1 field) and magnetization (M0) distributions. A series of T1-weighted gradient echo images were acquired and fitted to the extended Kety model with reversible or irreversible leakage, and the best model was selected using F-statistics. We applied this method to study the rat brain one hour following controlled cortical impact (mild to moderate TBI), and observed clear depiction of the BBB damage around the impact regions, which matched that outlined by Evans Blue extravasation. Unlike the relatively uniform T2 contrast showing cerebral edema, Ktrans shows a pronounced heterogeneous spatial profile in and around the impact regions, displaying a nonlinear relationship with T2. This improved Ktrans MRI method is also compatible with the use of high-sensitivity surface coil and the high-contrast two-coil arterial spin-labeling method for cerebral blood flow measurement, enabling more comprehensive investigation of the pathophysiology in TBI.

Detecting a Geometric Miss by Dynamic Contrast-enhanced Magnetic Resonance Imaging

Detecting a Geometric Miss by Dynamic Contrast-enhanced Magnetic Resonance Imaging

Evaluation of DCE-MRI postprocessing techniques to assess metastatic bone marrow in patients with prostate cancer

Dynamic contrast-enhanced magnetic resonance imaging was performed in control patients with normal bone marrow and patients with untreated bone metastases of prostate cancer (PCa). Perfusion data were assessed using region of interest-based and pixel-wise current standard postprocessing techniques (signal intensity pattern, increase in signal intensity, upslope, time to peak, extended Kety model, k-means clustering). Bone marrow perfusion is significantly increased in bone metastases of PCa compared to normal bone marrow. Pixel-wise kinetic modeling should be recommended to assess tumoral processes affecting bone marrow microcirculation.

DCE‐MRI model selection for investigating disruption of microvascular function in livers with metastatic disease

To evaluate the Akaike information criterion (AIC) model selection technique as a method for detecting differences in microvascular characteristics between tumorous and non-tumor liver tissue. The AIC was applied to six patient datasets with liver metastases to determine, on a per voxel basis, which of two physiologically plausible candidate models gave a more appropriate description of the data. The dual-input single-compartment Materne model, extended to incorporate a novel portal input function estimation method, was chosen to represent liver tissue and the single-input dual-compartment extended Kety model was used for tumor. Median AIC probabilities when comparing tumor versus liver and tumor versus tumor-margins were significantly different (P ≤ 0.01) in five of the six patient datasets. Comparisons between tumor margins and liver regions were significantly different in four datasets. Median AIC probabilities selected for the extended Kety model in all tumor regions, with the Materne model being progressively more probable through tumor margins into liver. We present a viable method for assessing the spatially varying microvascular characteristics of tumor-bearing livers, with possible applications in lesion detection, assessment of tumor invasion, and measurement of drug efficacy.

Repeated Positron Emission Tomography-Computed Tomography and Perfusion-Computed Tomography Imaging in Rectal Cancer: Fluorodeoxyglucose Uptake Corresponds With Tumor Perfusion

The purpose of this study was to analyze both the intratumoral fluorodeoxyglucose (FDG) uptake and perfusion within rectal tumors before and after hypofractionated radiotherapy. Rectal cancer patients, referred for preoperative hypofractionated radiotherapy (RT), underwent FDG-positron emission tomography (PET)-computed tomography (CT) and perfusion-CT (pCT) imaging before the start of hypofractionated RT and at the day of the last RT fraction. The pCT-images were analyzed using the extended Kety model, quantifying tumor perfusion with the pharmacokinetic parameters K(trans), v(e), and v(p). The mean and maximum FDG uptake based on the standardized uptake value (SUV) and transfer constant (K(trans)) within the tumor were correlated. Also, the tumor was subdivided into eight subregions and for each subregion the mean and maximum SUVs and K(trans) values were assessed and correlated. Furthermore, the mean FDG uptake in voxels presenting with the lowest 25% of perfusion was compared with the FDG uptake in the voxels with the 25% highest perfusion. The mean and maximum K(trans) values were positively correlated with the corresponding SUVs (ρ = 0.596, p = 0.001 and ρ = 0.779, p < 0.001). Also, positive correlations were found for K(trans) values and SUVs within the subregions (mean, ρ = 0.413, p < 0.001; and max, ρ = 0.540, p < 0.001). The mean FDG uptake in the 25% highest-perfused tumor regions was significantly higher compared with the 25% lowest-perfused regions (10.6% ± 5.1%, p = 0.017). During hypofractionated radiotherapy, stable mean (p = 0.379) and maximum (p = 0.280) FDG uptake levels were found, whereas the mean (p = 0.040) and maximum (p = 0.003) K(trans) values were found to significantly increase. Highly perfused rectal tumors presented with higher FDG-uptake levels compared with relatively low perfused tumors. Also, intratumor regions with a high FDG uptake demonstrated with higher levels of perfusion than regions with a relatively low FDG-uptake. Early after hypofractionated RT, stable FDG uptake levels were found, whereas tumor perfusion was found to significantly increase.

Dynamic contrast-enhanced MRI in ovarian cancer: Initial experience at 3 tesla in primary and metastatic disease

The aim of this study was to develop and demonstrate a methodology for dynamic contrast-enhanced MRI at 3 T in patients with advanced ovarian cancer and to report the results from pharmacokinetic modeling of the data. Nineteen patients with suspected advanced ovarian carcinoma (FIGO stage 3 or higher) were enrolled in this prospective study. Up to three marker lesions were identified: primary ovarian mass, omental ''cake'', and peritoneal deposits. Dynamic contrast-enhanced MRI was performed using a three-dimensional T(1)-weighted gradient-echo acquisition with a temporal resolution of 1.6 sec, following intravenous administration of 0.1 mmol/kg gadobutrol. Precontrast T(1) mapping, using an inversion-recovery fast gradient-echo sequence, was also performed. Imaging was completed in 18/19 patients, although two were subsequently excluded based on pathology results. Pharmacokinetic modeling of the data was performed according to the extended Kety model, using an arterial input function formed by concatenation of the Fritz-Hansen and Weinmann curves. No statistically significant differences were found between the results for the three marker lesions. In the future, this work will allow kinetic modeling results from ovarian dynamic contrast-enhanced MRI to be correlated with response to treatment. The high temporal resolution allows good characterization of the rapid contrast agent uptake in these vascular tumors.

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 T(1)-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 Akaike's 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.