Robust estimation of hemo-dynamic parameters in traditional DCE-MRI models.

PURPOSE: In dynamic contrast enhanced (DCE) MRI, separation of signal contributions from perfusion and leakage requires robust estimation of parameters in a pharmacokinetic model. We present and quantify the performance of a method to compute tissue hemodynamic parameters from DCE data using established pharmacokinetic models. METHODS: We propose a Bayesian scheme to obtain perfusion metrics from DCE MRI data. Initial performance is assessed through digital phantoms of the extended Tofts model (ETM) and the two-compartment exchange model (2CXM), comparing the Bayesian scheme to the standard Levenberg-Marquardt (LM) algorithm. Digital phantoms are also invoked to identify limitations in the pharmacokinetic models related to measurement conditions. Using computed maps of the extra vascular volume (ve) from 19 glioma patients, we analyze differences in the number of un-physiological high-intensity ve values for both ETM and 2CXM, using a one-tailed paired t-test assuming un-equal variance. RESULTS: The Bayesian parameter estimation scheme demonstrated superior performance over the LM technique in the digital phantom simulations. In addition, we identified limitations in parameter reliability in relation to scan duration for the 2CXM. DCE data for glioma and cervical cancer patients was analyzed with both algorithms and demonstrated improvement in image readability for the Bayesian method. The Bayesian method demonstrated significantly fewer non-physiological high-intensity ve values for the ETM (p<0.0001) and the 2CXM (p<0.0001). CONCLUSION: We have demonstrated substantial improvement of the perceptive quality of pharmacokinetic parameters from advanced compartment models using the Bayesian parameter estimation scheme as compared to the LM technique.

Performance of a fast and high-resolution multi-echo spin-echo sequence for prostate T2 mapping across multiple systems.

PURPOSE: To evaluate the performance of a multi-echo spin-echo sequence with k-t undersampling scheme (k-t T2 ) in prostate cancer. METHODS: Phantom experiments were performed at five systems to estimate the bias, short-term repeatability, and reproducibility across all systems expressed with the within-subject coefficient of variation (wCV). Monthly measurements were performed on two systems for long-term repeatability estimation. To evaluate clinical repeatability, two T2 maps (voxel size 0.8 × 0.8 × 3 mm3 ; 5 min) were acquired at separate visits on one system for 13 prostate cancer patients. Repeatability was assessed per patient in relation to spatial resolution. T2 values were compared for tumor, peripheral zone, and transition zone. RESULTS: Phantom measurements showed a small bias (median = -0.9 ms) and good short-term repeatability (median wCV = 0.5%). Long-term repeatability was 0.9 and 1.1% and reproducibility between systems was 1.7%. The median bias observed in patients was -1.1 ms. At voxel level, the median wCV was 15%, dropping to 4% for structures of 0.5 cm3 . The median tumor T2 values (79 ms) were significantly lower (P < 0.001) than in the peripheral zone (149 ms), but overlapped with the transition zone (91 ms). CONCLUSIONS: Reproducible T2 mapping of the prostate is feasible with good spatial resolution in a clinically reasonable scan time, allowing reliable measurement of T2 in structures as small as 0.5 cm3 . Magn Reson Med 79:1586-1594, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Diffusion-weighted magnetic resonance imaging during radiotherapy of locally advanced cervical cancer--treatment response assessment using different segmentation methods.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) and the derived apparent diffusion coefficient (ADC) value has potential for monitoring tumor response to radiotherapy (RT). Method used for segmentation of volumes with reduced diffusion will influence both volume size and observed distribution of ADC values. This study evaluates: 1) different segmentation methods; and 2) how they affect assessment of tumor ADC value during RT. MATERIAL AND METHODS: Eleven patients with locally advanced cervical cancer underwent MRI three times during their RT: prior to start of RT (PRERT), two weeks into external beam RT (WK2RT) and one week prior to brachytherapy (PREBT). Volumes on DW-MRI were segmented using three semi-automatic segmentation methods: "cluster analysis", "relative signal intensity (SD4)" and "region growing". Segmented volumes were compared to the gross tumor volume (GTV) identified on T2-weighted MR images using the Jaccard similarity index (JSI). ADC values from segmented volumes were compared and changes of ADC values during therapy were evaluated. RESULTS: Significant difference between the four volumes (GTV, DWIcluster, DWISD4 and DWIregion) was found (p < 0.01), and the volumes changed significantly during treatment (p < 0.01). There was a significant difference in JSI among segmentation methods at time of PRERT (p < 0.016) with region growing having the lowest JSIGTV (mean± sd: 0.35 ± 0.1), followed by the SD4 method (mean± sd: 0.50 ± 0.1) and clustering (mean± sd: 0.52 ± 0.3). There was no significant difference in mean ADC value compared at same treatment time. Mean tumor ADC value increased significantly (p < 0.01) for all methods across treatment time. CONCLUSION: Among the three semi-automatic segmentations of hyper-intense intensities on DW-MR images implemented, cluster analysis and relative signal thresholding had the greatest similarity to the clinical tumor volume. Evaluation of mean ADC value did not depend on segmentation method.

Tracer kinetic model selection for dynamic contrast-enhanced magnetic resonance imaging of locally advanced cervical cancer.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a unique capability to probe tumour microvasculature. Different analysis of the acquired data will possibly lead to different conclusions. Therefore, the objective of this study was to investigate under which conditions the Tofts (TM), extended Tofts (ETM), compartmental tissue uptake model (C-TU) and 2-compartment exchange model (2CXM) were the optimal tracer kinetic models (TKMs) for the analysis of DCE-MRI in patients with cervical cancer. MATERIAL AND METHODS: Ten patients with locally advanced cervical cancer (FIGO: IIA/IIB/IIIB/IVA - 1/5/3/1) underwent DCE-MRI prior to radiotherapy. From the two-parameter TM it was possible to extract the forward volume transfer constant (K(trans)) and the extracellular-extravascular volume fraction (ve). From the three-parameter ETM, additionally the plasma volume fraction (vp) could be extracted. From the three-parameter C-TU it was possible to extract information about the blood flow (Fp), permeability-surface area product (PS) and vp. Finally, the four-parameter 2CXM extended the C-TU to include ve. For each voxel, corrected Akaike information criterion (AICc) values were calculated, taking into account both the goodness-of-fit and the number of model parameters. The optimal model was defined as the model with the lowest AICc. RESULTS: All four TKMs were the optimal model in different contiguous regions of the cervical tumours. For the 24 999 analysed voxels, the TM was optimal in 17.0%, the ETM was optimal in 2.2%, the C-TU in 23.4% and the 2CXM was optimal in 57.3%. Throughout the tumour, a high correlation was found between K(trans)(TM) and Fp(2CXM), ρ = 0.91. CONCLUSION: The 2CXM was most often optimal in describing the contrast agent enhancement of pre-treatment cervical cancers, although this model broke down in a subset of the tumour voxels where overfitting resulted in non-physiological parameter estimates. Due to the possible overfitting of the 2CXM, the C-TU was found more robust and when 2CXM was excluded from comparison the C-TU was the preferred model.

Correction of diffusion-weighted magnetic resonance imaging for brachytherapy of locally advanced cervical cancer.

BACKGROUND: Geometrical distortion is a major obstacle for the use of echo planar diffusion-weighted magnetic resonance imaging (DW-MRI) in planning of radiotherapy. This study compares geometrical distortion correction methods of DW-MRI at time of brachytherapy (BT) in locally advanced cervical cancer patients. MATERIAL AND METHODS: In total 21 examinations comprising DW-MRI, dual gradient echo (GRE) for B0 field map calculation and T2-weighted (T2W) fat-saturated MRI of eight patients with locally advanced cervical cancer were acquired during BT with a plastic tandem and ring applicator in situ. The ability of B0 field map correction (B0M) and deformable image registration (DIR) to correct DW-MRI geometric image distortion was compared to the non-corrected DW-MRI including evaluation of apparent diffusion coefficient (ADC) for the gross tumor volume (GTV). RESULTS: Geometrical distortion correction decreased tandem displacement from 3.3 ± 0.9 mm (non-corrected) to 2.9 ± 1.0 mm (B0M) and 1.9 ± 0.6 mm (DIR), increased mean normalized cross-correlation from 0.69 ± 0.1 (non- corrected) to 0.70 ± 0.10 (B0M) and 0.77 ± 0.1 (DIR), and increased the Jaccard similarity coefficient from 0.72 ± 0.1 (non-corrected) to 0.73 ± 0.06 (B0M) and 0.77 ± 0.1 (DIR). For all parameters only DIR corrections were significant (p < 0.05). ADC of the GTV did not change significantly with either correction method. CONCLUSION: DIR significantly improved geometrical accuracy of DW-MRI, with remaining residual uncertainties of less than 2 mm, while no significant improvement was seen using B0 field map correction.

Voxelwise comparison of perfusion parameters estimated using dynamic contrast enhanced (DCE) computed tomography and DCE-magnetic resonance imaging in locally advanced cervical cancer.

PURPOSE: Dynamic contrast enhanced (DCE) imaging has gained interest as an imaging modality for assessment of tumor characteristics and response to cancer treatment. However, for DCE-magnetic resonance imaging (MRI) tissue contrast enhancement may vary depending on imaging sequence and temporal resolution. The aim of this study is to compare DCE-MRI to DCE-computed tomography (DCE-CT) as the gold standard. MATERIAL AND METHODS: Thirteen patients with advanced cervical cancer were scanned once prior to chemo-radiation and during chemo-radiation with DCE-CT and -MRI in immediate succession. A total of 22 paired DCE-CT and -MRI scans were acquired for comparison. Kinetic modeling using the extended Tofts model was applied to both image series. Furthermore the similarity of the spatial distribution was evaluated using a Γ analysis. The correlation between the two imaging techniques was evaluated using Pearson's correlation and the parameter means were compared using a Student's t-test (p < 0.05). RESULTS: A significant positive correlation between DCE-CT and -MRI was found for all kinetic parameters. The results showing the best correlation with the DCE-CT-derived parameters were obtained using a population-based input function for MRI. The median Pearson's correlations were: volume transfer constant K(trans) (r = 0.9), flux rate constant kep (r = 0.77), extracellular volume fraction ve (r = 0.58) and blood plasma volume fraction vp (r = 0.83). All quantitative parameters were found to be significantly different as estimated by DCE-CT and -MRI. The Γ analysis in normalized maps revealed that 45% of the voxels failed to find a voxel with the corresponding value allowing for an uncertainty of 3 mm in position and 3% in value (Γ3,3). By reducing the criteria, the Γ-failure rates were: Γ3,5 (37% failure), Γ3,10 (26% failure) and at Γ3,15 (19% failure). CONCLUSION: Good to excellent correlations but significant bias was found between DCE-CT and -MRI. Both the Pearson's correlation and the Γ analysis proved that the spatial information was similar when analyzing the two sets of DCE data using the extended Tofts model. Improvement of input function sampling is needed to improve kinetic quantification using DCE-MRI.

Quantitative liver ADC measurements using diffusion-weighted MRI at 3 Tesla: evaluation of reproducibility and perfusion dependence using different techniques for respiratory compensation.

OBJECT: Diffusion weighted imaging (DWI) of the liver suffers from low signal to noise making 3 Tesla (3 T) an attractive option, but 3 T data is scarce. It was the aim to study the influence of different b values and respiratory compensation methods (RCM) on the apparent diffusion coefficient (ADC) level and on ADC reproducibility at 3 T. MATERIALS AND METHODS: Ten healthy volunteers and 12 patients with malignant liver lesions underwent repeated (2-22 days) breathhold, free-breathing and respiratory triggered DWI at 3 T using b values between 0 and 1,000 s/mm(2). RESULTS: The ADCs changed up to 150% in healthy livers and up to 48% in malignant lesions depending on b value combinations. Best ADC reproducibility in healthy livers were obtained with respiratory triggering (95% limits of agreement: ±0.12) and free-breathing (±0.14). In malignant lesions equivalent reproducibility was obtained with less RCM dependence. The use of a lower maximum b value (b = 500) decreased reproducibility (±0.14 to ±0.32) in both normal liver and malignant lesions. CONCLUSION: Large differences in absolute ADC values and reproducibility caused by varying combinations of clinically realistic b values were demonstrated. Different RCMs caused smaller differences. Lowering maximum b value to 500 increased limits of agreement up to a factor of two. Serial ADC changes larger than approximately 15% can be detected confidently on an individual basis in both malignant lesions and normal liver parenchyma at 3 T using appropriate b values and respiratory compensation.

Intensity profile based measurement of prostate gold markers influence on 1.5 and 3T diffusion-weighted MR images.

BACKGROUND AND PURPOSE: In this study the influence of fiducial markers (FMs) on diffusion-weighted (DW) magnetic resonance images was investigated by measuring the intensity variations due to the artefact from the FM image reconstruction. MATERIAL AND METHODS: DW- and reference T1W images were acquired of an Agar-gel phantom containing two fixed cylindrical FMs, with a 1.5- and 3T MR scanner. The center of gravity (CoG) positions of the manually segmented FM artefacts (FMA) and the size of FMAs in x-, y- and z direction were measured in the two corresponding image sets, based on the intensity changes caused by the FM reconstruction. Also, a similarity measure, the Dice similarity coefficient (DSC), of the segmented FMAs in the two image sets was calculated. RESULTS: The mean shift of the CoG of the manually segmented FMAs in the phase encoding (PE) and the two orthogonal directions, respectively, was: 1.5T/3T; 0.3 ± 0.1/0.5 ± 0.3 cm and 1.5T/3T; 0.1 ± 0.1/0.1 ± 0.1 cm. The largest shift was observed in the 3T DW images for FMs aligned with the long axis orthogonal to the PE direction (0.9 ± 0.1 cm). The mean size of the FMA in the PE- and the two orthogonal directions, respectively, was: 1.5T/3T; 1.7 ± 0.5/1.3 ± 0.1 cm, and 1.5T/3T; 0.9 ± 0.3/1.0 ± 0.2 cm. The mean DSC value of the segmented artefact volumes in the DW- vs. T1W images were 21% and 5% for the 1.5- and 3.0T MR scanner, respectively. CONCLUSIONS: This study has shown that both the size and displacement of the FMAs increase in the PE direction on DW images. The larger shifts were observed for FMs positioned with the long axis orthogonal to the PE direction. Measurements obtained for different b-values gave consistent results.

Apparent diffusion coefficients in GEC ESTRO target volumes for image guided adaptive brachytherapy of locally advanced cervical cancer.

BACKGROUND AND PURPOSE: T2 weighted MRI is recommended for image guided adaptive brachytherapy (IGABT) in cervical cancer. Diffusion weighted imaging (DWI) and the derived apparent diffusion coefficient (ADC) may add additional biological information on tumour cell density. The purpose of this study was to evaluate the distribution of the ADC within target volumes as recommended by GEC-ESTRO: Gross Tumour Volume at BT (GTV(BT)), High-Risk Clinical Tumour Volume (HR-CTV) and Intermediate-Risk Clinical Target Volume (IR-CTV) and to evaluate the change of diffusion between fractions of IGABT. MATERIAL AND METHODS: Fifteen patients with locally advanced cervical cancer were examined by MRI before their first (BT1) and second (BT2) fraction of IGABT, resulting in a total of 30 MR examinations including both T2 weighted and DWI sequences. The Apparent Diffusion Coefficient (ADC) was calculated by use of three levels of b-values (0, 600, 1000 s/mm(2)). ADC maps were constructed and fused with the GEC ESTRO target contours. The mean ADC value within each target volume was calculated. Furthermore, volumes of low diffusion (ADC(low)) were defined based on an ADC threshold of 1.2 × 10(-3) mm(2)/s, and overlap with target volumes was evaluated. Change of ADC level in target volumes and change of ADC(low) volume from BT1 to BT2 was also evaluated. RESULTS: The mean ADC was significantly lower in GTV(BT) than in HR-CTV (p<0.001) which again was significantly lower than in IR-CTV (p<0.001). There was no significant change of the ADC(low) volume or ADC level within each target structure between BT1 and BT2 (p=0.242). All three GEC-ESTRO volumes contained volumes with low diffusion. The GTV(BT) contained 37.2% volume of low diffusion, HR-CTV 20.3% and IR-CTV 10.8%. CONCLUSION: With DWI we were able to find a significant difference in ADC-values for the three different GEC ESTRO targets. This supports the assumption that the target volumes used for dose prescription in IGABT contain tissues with different characteristics, with the tumour (GTV(BT)) being the volume with the lowest diffusion. No significant changes were found from BT1 to BT2 indicating that changes of ADC level and volumes are stable at the time of BT. Further studies are needed to evaluate the role of DWI in target contouring and dose prescription for IGABT.

Apparent Diffusion Coefficient (ADC) as a quantitative parameter in diffusion weighted MR imaging in gynecologic cancer: Dependence on b-values used.

BACKGROUND: Diffusion weighted imaging (DWI) has gained interest as an imaging modality for assessment of tumor extension and response to cancer treatment. The purpose of this study is to assess the impact of the choice of b-values on the calculation of the Apparent Diffusion Coefficient (ADC) for locally advanced gynecological cancer and to estimate a stable interval of diffusion gradients that allows for best comparison of the ADC between patients and institutions. MATERIAL AND METHODS: Six patients underwent a high resolution single shot EPI based DWI scan with 16 different diffusion gradients on a 3 Tesla Philips Achieva MR-scanner. Data analysis was performed by applying a monoexponential and a biexponential model to the acquired data. The biexponential function models the effect of both perfusion and diffusion. RESULTS AND CONCLUSION: ADC changes of up to 40% were seen with the use of different b-values. Using a lower b-value ≥ 150 s/mm(2) and an upper b-value ≥ 700 s/mm(2) limited the variation to less that 10% from the reference ADC value. By eliminating the contribution of perfusion the uncertainty of quantitative ADC values were significantly reduced.

Applicator reconstruction in MRI 3D image-based dose planning of brachytherapy for cervical cancer.

BACKGROUND AND PURPOSE: To elaborate a method for applicator reconstruction for MRI-based brachytherapy for cervical cancer. MATERIALS AND METHODS: Custom-made plastic catheters with a copper sulphate solution were made for insertion in the source channels of MR-CT compatible applicators: plastic and titanium tandem ring applicators, and titanium needles. The applicators were CT and MR scanned in a phantom for accurate 3D assessment of applicator visibility and geometry. A reconstruction method was developed and evaluated in 19 patient MR examinations with ring applicator (plastic: 14, titanium: 5). MR applicator reconstruction uncertainties related to inter-observer variation were evaluated. RESULTS: The catheters were visible in the plastic applicator on T1-weighted images in phantom and in 14/14 clinical applications. On T2-weighted images, the catheters appeared weaker but still visible in phantom and in 13/14 MR clinical applications. In the titanium applicator, the catheters could not be separated from the artifacts from the applicator itself. However, these artifacts could be used to localize both titanium ring applicator (5/5 clinical applications) and needles (6/6 clinical applications). Standard deviations of inter-observer differences were below 2 mm in all directions. CONCLUSION: 3D applicator reconstruction based on MR imaging could be performed for plastic and titanium applicators. Plastic applicators proved well to be suited for MRI-based reconstruction. For improved practicability of titanium applicator reconstruction, development of MR applicator markers is essential. Reconstruction of titanium applicator and needles at 1.5 T MR requires geometric evaluations in phantoms before using the applicator in patients.

MRI-guided 3D optimization significantly improves DVH parameters of pulsed-dose-rate brachytherapy in locally advanced cervical cancer.

PURPOSE: To compare dose-volume histogram parameters of standard Point A and magnetic resonance imaging-based three-dimensional optimized dose plans in 21 consecutive patients who underwent pulsed-dose-rate brachytherapy (PDR-BT) for locally advanced cervical cancer. METHODS AND MATERIALS: All patients received external beam radiotherapy (elective target dose, 45 Gy in 25-30 fractions; tumor target dose, 50-60 Gy in 25-30 fractions). PDR-BT was applied with a tandem-ring applicator. Additional ring-guided titanium needles were used in 4 patients and a multichannel vaginal cylinder in 2 patients. Dose planning was done using 1.5 Tesla T(1)-weighted and T(2)-weighted paratransversal magnetic resonance imaging scans. T(1)-weighted visible oil-containing tubes were used for applicator reconstruction. The prescribed standard dose for PDR-BT was 10 Gy (1 Gy/pulse, 1 pulse/h) for two to three fractions to reach a physical dose of 80 Gy to Point A. The total dose (external beam radiotherapy plus brachytherapy) was normalized to an equivalent dose in 2-Gy fractions using alpha/beta = 10 Gy for tumor, alpha/beta = 3 Gy for normal tissue, and a repair half-time of 1.5 h. The goal of optimization was dose received by 90% of the target volume (D(90)) of > or =85 Gy(alpha/beta10) in the high-risk clinical target volume (cervix and remaining tumor at brachytherapy), but keeping the minimal dose to 2 cm(3) of the bladder and rectum/sigmoid at <90 and <75 Gy(alpha/beta3), respectively. RESULTS: Using three-dimensional optimization, all dose-volume histogram constraints were met in 16 of 21 patients compared with 3 of 21 patients with two-dimensional library plans (p < 0.001). Optimization increased the minimal target dose (D(100)) of the high-risk clinical target volume (p < 0.007) and decreased the minimal dose to 2 cm(3) for the sigmoid significantly (p = 0.03). For the high-risk clinical target volume, D(90) was 91 +/- 8 Gy(alpha/beta10) and D(100) was 76 +/- 5 Gy(alpha/beta10). The minimal dose to 2 cm(3) for the bladder, rectum, and sigmoid was 73 +/- 6, 67 +/- 6, and 69 +/- 6 Gy(alpha/beta3), respectively. CONCLUSION: The results of our study have shown that magnetic resonance imaging-guided optimization of PDR-BT for locally advanced cervical cancer significantly improved the dose-volume histogram parameters.