Oliver J. Gurney-Champion

Minimizing the Acquisition Time for Intravoxel Incoherent Motion Magnetic Resonance Imaging Acquisitions in the Liver and Pancreas

ObjectivesThe aim of this study was to determine the combination of b-values and signal averages for diffusion-weighted image acquisitions that render the minimum acquisition time necessary to obtain values of the intravoxel incoherent motion (IVIM) model parameters in vivo in the pancreas or liver with acceptable reproducibility. Materials and MethodsFor 16 volunteers, diffusion-weighted images, with 14 b-values and 9 acquisitions per b-value, were acquired in 2 scan sessions. The IVIM model was fitted to data from lesion-sized regions of interest (ROIs) (1.7 cm3) as well as organ-sized ROIs in the pancreas and liver. By deleting data during analyzes, the IVIM model parameters, D and f, could be determined as a function of the number of b-values as well as the number of measurements per b-value taken along. For the IVIM model parameters, we examined the behavior reproducibility, in the form of the within-subject coefficient of variation (CVw), as a function of the amount of data taken along in the fits. Finally, we determined the minimum acquisition time required as a function of CVw. ResultFor the lesion-sized ROI, the intersession CVws were 8%/46% and 13%/55% for D/f in the pancreas and liver, respectively, when all data were taken along. For 1.2 times larger CVws, acquisition in the pancreas could be done in 5:15 minutes using 9 acquisitions per b-value at b = 0, 30, 50, 65, 100, 375, and 500 mm−2s and for the liver in 2:15 using 9 acquisitions per b-value at b = 0, 40, and 500 mm−2s. ConclusionsAcquiring 7 b-values in the pancreas and 3 b-values in the liver only decreases the reproducibility by 20% compared with an acquisition with 14 b-values. The understanding of the behavior of reproducibility as a function of b-values and acquisitions per b-values scanned will help researchers select the shortest IVIM protocol.

Considerable interobserver variation in delineation of pancreatic cancer on 3DCT and 4DCT: a multi-institutional study.

BackgroundThe delineation of pancreatic tumors on CT is challenging. In this study, we quantified the interobserver variation for pancreatic tumor delineation on 3DCT as well as on 4DCT.MethodsEight observers (radiation oncologists) from six institutions delineated pancreatic tumors of four patients with (borderline) resectable pancreatic cancer. The study consisted of two stages. In the 3DCT-stage, the gross tumor volume (GTV) was delineated on a contrast-enhanced scan. In the 4DCT-stage, the internal GTV (iGTV) was delineated, accounting for the respiratory motion. We calculated the volumes of the (i)GTV, the overlap of the delineated volumes (expressed as generalized conformity index: CIgen), the local observer variation (local standard deviation: SD) and the overall observer variation (overall SD). We compared these results between GTVs and iGTVs. Additionally, observers were asked to fill out a questionnaire concerning the difficulty of the delineation and their experience in delineating pancreatic tumors.ResultsThe ratios of the largest to the smallest delineated GTV and iGTV within the same patient were 6.8 and 16.5, respectively. As the iGTV incorporates the GTV during all respiratory phases, the mean volumes of the iGTV (40.07 cm3) were larger than those of the GTV (29.91 cm3). For all patients, CIgen was larger for the iGTV than for the GTV. The mean overall observer variation (root-mean-square of all local SDs over four patients) was 0.63 cm and 0.80 cm for GTV and iGTV, respectively. The largest local observer variations were seen close to biliary stents and suspicious pathological enlarged lymph nodes, as some observers included them and some did not. This variation was more pronounced for the iGTV than for the GTV. The observers rated the 3DCT-stage and 4DCT-stage equally difficult and treated on average three to four pancreatic cancer patients per year.ConclusionsA considerable interobserver variation in delineation of pancreatic tumors was observed. This variation was larger for 4D than for 3D delineation. The largest local observer variation was found around biliary stents and suspicious pathological enlarged lymph nodes.

Abdominal organ motion during inhalation and exhalation breath-holds: pancreatic motion at different lung volumes compared

PURPOSE Contrary to what is commonly assumed, organs continue to move during breath-holding. We investigated the influence of lung volume on motion magnitude during breath-holding and changes in velocity over the duration of breath-holding. MATERIALS AND METHODS Sixteen healthy subjects performed 60-second inhalation breath-holds in room-air, with lung volumes of ∼100% and ∼70% of the inspiratory capacity, and exhalation breath-holds, with lung volumes of ∼30% and ∼0% of the inspiratory capacity. During breath-holding, we obtained dynamic single-slice magnetic-resonance images with a time-resolution of 0.6s. We used 2-dimensional image correlation to obtain the diaphragmatic and pancreatic velocity and displacement during breath-holding. RESULTS Organ velocity was largest in the inferior-superior direction and was greatest during the first 10s of breath-holding, with diaphragm velocities of 0.41mm/s, 0.29mm/s, 0.16mm/s and 0.15mm/s during BH100%, BH70%, BH30% and BH0%, respectively. Organ motion magnitudes were larger during inhalation breath-holds (diaphragm moved 9.8 and 9.0mm during BH100% and BH70%, respectively) than during exhalation breath-holds (5.6 and 4.3mm during BH30% and BH0%, respectively). CONCLUSION Using exhalation breath-holds rather than inhalation breath-holds and delaying irradiation until after the first 10s of breath-holding may be advantageous for irradiation of abdominal tumors.

Addition of MRI for CT-based pancreatic tumor delineation: a feasibility study

Abstract Purpose: To assess the effect of additional magnetic resonance imaging (MRI) alongside the planning computed tomography (CT) scan on target volume delineation in pancreatic cancer patients. Material and methods: Eight observers (radiation oncologists) from six institutions delineated the gross tumor volume (GTV) on 3DCT, and internal GTV (iGTV) on 4DCT of four pancreatic cancer patients, while MRI was available in a second window (CT + MRI). Variations in volume, generalized conformity index (CIgen), and overall observer variation, expressed as standard deviation (SD) of the distances between delineated surfaces, were analyzed. CIgen is a measure of overlap of the delineated iGTVs (1 = full overlap, 0 = no overlap). Results were compared with those from an earlier study that assessed the interobserver variation by the same observers on the same patients on CT without MRI (CT-only). Results: The maximum ratios between delineated volumes within a patient were 6.1 and 22.4 for the GTV (3DCT) and iGTV (4DCT), respectively. The average (root-mean-square) overall observer variations were SD = 0.41 cm (GTV) and SD = 0.73 cm (iGTV). The mean CIgen was 0.36 for GTV and 0.37 for iGTV. When compared to the iGTV delineated on CT-only, the mean volumes of the iGTV on CT + MRI were significantly smaller (32%, Wilcoxon signed-rank, p < .0005). The median volumes of the iGTV on CT + MRI were included for 97% and 92% in the median volumes of the iGTV on CT. Furthermore, CT + MRI showed smaller overall observer variations (root-mean-square SD = 0.59 cm) in six out of eight delineated structures compared to CT-only (root-mean-square SD = 0.72 cm). However, large local observer variations remained close to biliary stents and pathological lymph nodes, indicating issues with instructions and instruction compliance. Conclusions: The availability of MRI images during target delineation of pancreatic cancer on 3DCT and 4DCT resulted in smaller target volumes and reduced the interobserver variation in six out of eight delineated structures.

Quantitative assessment of biliary stent artifacts on MR images: Potential implications for target delineation in radiotherapy

PURPOSE Biliary stents may cause susceptibility artifacts, gradient-induced artifacts, and radio frequency (RF) induced artifacts on magnetic resonance images, which can hinder accurate target volume delineation in radiotherapy. In this study, the authors investigated and quantified the magnitude of these artifacts for stents of different materials. METHODS Eight biliary stents made of nitinol, platinum-cored nitinol, stainless steel, or polyethylene from seven vendors, with different lengths (57-98 mm) and diameters (3.0-11.7 mm), were placed in a phantom. To quantify the susceptibility artifacts sequence-independently, ΔB0-maps and T2∗-maps were acquired at 1.5 and 3 T. To study the effect of the gradient-induced artifacts at 3 T, signal decay in images obtained with maximum readout gradient-induced artifacts was compared to signal decay in reference scans. To quantify the RF induced artifacts at 3 T, B1-maps were acquired. Finally, ΔB0-maps and T2∗-maps were acquired at 3 T of two pancreatic cancer patients who had received platinum-cored nitinol biliary stents. RESULTS Outside the stent, susceptibility artifacts dominated the other artifacts. The stainless steel stent produced the largest susceptibility artifacts. The other stents caused decreased T2∗ up to 5.1 mm (1.5 T) and 8.5 mm (3 T) from the edge of the stent. For sequences with a higher bandwidth per voxel (1.5 T: BWvox > 275 Hz/voxel; 3 T: BWvox > 500 Hz/voxel), the B0-related susceptibility artifacts were negligible (<0.2 voxels). The polyethylene stent showed no artifacts. In vivo, the changes in B0 and T2∗ induced by the stent were larger than typical variations in B0 and T2∗ induced by anatomy when the stent was at an angle of 30° with the main magnetic field. CONCLUSIONS Susceptibility artifacts were dominating over the other artifacts. The magnitudes of the susceptibility artifacts were determined sequence-independently. This method allows to include additional safety margins that ensure target irradiation.

Revisiting the Potential of Alternating Repetition Time Balanced Steady-State Free Precession Imaging of the Abdomen at 3 T.

ObjectiveThe aim was to investigate the value of optimized 3-dimensional alternating repetition time balanced steady-state free precession (ATR-SSFP), as an alternative to conventional segmented balanced steady-state free precession (bSSFP) with fat suppression prepulse (FS-bSSFP), in single breath-hold abdominal magnetic resonance imaging at 3 T. MethodsBloch simulations were performed to determine the optimal flip angle (FA = 1–90 degrees) and &tgr; (1–3) with respect to signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) between abdominal organs for ATR-SSFP. These were corroborated by phantom measurements for different T1/T2 values (5–47) as well as in a healthy volunteer. In addition, fat suppression efficiency was studied using phantom and volunteer measurements. The effect of resolution on image quality was studied in a healthy volunteer. Using the optimal settings, ATR-SSFP images as well as FS-bSSFP images were obtained in 15 pancreatic cancer patients. For 10 structures of interest, the signal ratio with respect to the pancreas was computed and compared between both sequences. Finally, 10 items on image quality (fat suppression, artifacts, and sharpness) and tissue conspicuity (ducts, vessels, and duodenum) were scored by 2 abdominal radiologists for both image sequences. ResultsThe results of simulations, phantom measurements, and volunteer measurements showed that, considering scan time, fat suppression, and clinical relevance, the ideal settings for ATR-SSFP were as follows: &tgr; = 3; TR1 = 3.46 milliseconds; radiofrequency phase cycling 0, 180, 180, 0 degrees; and FA = 13–16 degrees (highest SNR) and 24–26 degrees (highest CNR). The optimized feasible additional settings implemented for patient scans were FA = 18 degrees and resolution = 1.4 × 1.4 × 1.4 mm3. In patients, the signal ratios of both ATR-SSFP and FS-bSSFP were comparable and had a T2-like contrast behavior, although more accentuated in ATR-SSFP. The ATR-SSFP scored significantly higher than FS-bSSFP for 9 of 10 items scored. ConclusionsFor single breath-hold abdominal imaging at 3 T, ATR-SSFP performs best with &tgr; = 3 and an FA between 13 degrees (highest SNR) and 26 degrees (highest CNR). The scoring of both abdominal radiologists indicated that, at &tgr; = 3, FA = 18 degrees, and 1.4 × 1.4 × 1.4 mm3 resolution, ATR-SSFP was preferred over conventional FS-bSSFP with similar settings.

Comparison of six fit algorithms for the intra-voxel incoherent motion model of diffusion-weighted magnetic resonance imaging data of pancreatic cancer patients

The intravoxel incoherent motion (IVIM) model for diffusion-weighted imaging (DWI) MRI data bears much promise as a tool for visualizing tumours and monitoring treatment response. To improve the currently poor precision of IVIM, several fit algorithms have been suggested. In this work, we compared the performance of two Bayesian IVIM fit algorithms and four other IVIM fit algorithms for pancreatic cancer imaging. DWI data were acquired in 14 pancreatic cancer patients during two MRI examinations. Three different measures of performance of the fitting algorithms were assessed: (i) uniqueness of fit parameters (Spearman’s rho); (ii) precision (within-subject coefficient of variation, wCV); and (iii) contrast between tumour and normal-appearing pancreatic tissue. For the diffusivity D and perfusion fraction f, a Bayesian fit (IVIM-Bayesian-lin) offered the best trade-off between tumour contrast and precision. With the exception for IVIM-Bayesian-lin, all algorithms resulted in a very poor precision of the pseudo-diffusion coefficient D* with a wCV of more than 50%. The pseudo-diffusion coefficient D* of the Bayesian approaches were, however, significantly correlated with D and f. Therefore, the added value of fitting D* was considered limited in pancreatic cancer patients. The easier implemented least squares fit with fixed D* (IVIM-fixed) performed similar to IVIM-Bayesian-lin for f and D. In conclusion, the best performing IVIM fit algorithm was IVM-Bayesian-lin, but an easier to implement least squares fit with fixed D* performs similarly in pancreatic cancer patients.

A tri-exponential model for intravoxel incoherent motion analysis of the human kidney : In silico and during pharmacological renal perfusion modulation

In the kidneys, there is both blood flow through the capillaries and flow of pre-urine through the tubuli and collecting ducts. We hypothesized that diffusion-weighted (DW) MRI measures both blood and pre-urine flow when using a tri-exponential intravoxel incoherent motion (IVIM) model. Our aim was to systematically investigate and optimize tri-exponential IVIM-analysis for the kidney and test its sensitivity to renal perfusion changes in humans. The tri-exponential fit probes the diffusion coefficient (D), the intermediate (D*i) and fast (D*f) pseudo-diffusion coefficients, and their signal fractions, fD, fi and ff. First, we studied the effects of fixing the D*-coefficients of the tri-exponential fit using in silico simulations. Then, using a 3T MRI scanner, DW images were acquired in healthy subjects (18-24 years) and we assessed the within-subject coefficient of variation (wsCV, n=6). Then, renal perfusion was modulated by Angiotensin II infusion during which DW imaging of the kidneys and phase contrast MRI of the renal artery was performed (n=8). Radioisotope clearing tests were used to assess the glomerular filtration rate. Simulations showed that fixing the D*-coefficients - which could potentially increase the fit stability - in fact decreased the precision of the model. Changes in D*-coefficients were translated into the f-parameters instead. Fixing D*-coefficients resulted in a stronger response of the fit parameters to the intervention. Using this model, the wsCVs for D, fD, fi and ff were 2.4%, 0.8%, 3.5%, 19.4% respectively. fi decreased by 14% (p=0.059) and ff increased by 32% (p=0.004) between baseline and maximal Angiotensin II dose. ff inversely correlated to renal plasma flow (R=-0.70, p<0.01) and fi correlated to glomerular filtration rate (R=0.39, p=0.026). We validated a kidney-specific method for IVIM analysis using a tri-exponential model. The model is able to track renal perfusion changes induced by Angiotensin II.

MO-FG-BRA-09: Towards an Optimal Breath-Holding Procedure for Radiotherapy: Differences in Organ Motion During Inhalation and Exhalation Breath-Holds

PURPOSE Breath-holding (BH) is often used to reduce organ motion during radiotherapy. The aim of this study was to determine the differences in pancreatic and diaphragmatic motion during BH between inhalation and exhalation BHs with variable lung volumes and to investigate whether motion increases/decreases during BH. METHODS Sixteen healthy volunteers were asked to perform four different 60-second BHs, from fully inflated to fully deflated lungs (i.e. lung volumes of: 100%, ∼70%, ∼30% and 0% of inspiratory capacity) three times (total of 192 BHs). During each BH, we obtained single-slice (coronal) magnetic-resonance scans with spatial resolution 0.93×0.93×8.0 mm3 and temporal resolution 0.6 s. We used 2-dimensional image correlation to obtain the motion of pancreatic head and diaphragm during BH. Motion magnitude in inferior-superior direction was obtained by determining the maximum displacement during BH. RESULTS Pancreatic and diaphragmatic drifts occurred during BH and were mostly in the superior direction. We observed significantly smaller pancreatic and diaphragmatic motion magnitudes in inferior-superior direction during exhalation BHs (BH30% and BH0% ) compared to inhalation BHs (BH100% and BH70% ). The mean motion magnitudes of the pancreatic head were 7.0, 6.5, 4.4 and 4.2 mm during BH100% , BH70% , BH30% and BH0% , respectively, and mean BH durations were 59.9, 59.1, 59.0 and 52.7 s. For the diaphragm, mean motion magnitudes were 9.8, 9.0, 5.6 and 4.3 mm, respectively. When considering 30-second BHs, as often used in the clinic, the motion was most pronounced during the first 10 s and excluding these from the analysis (yielding an effective BH period of 20 s) significantly reduced (P≤0.002) organ motion. CONCLUSION Organ motion was significantly smaller during exhalation BHs compared to inhalation BHs. Also, motion was largest at the start of BH. Hence, waiting for 10 s may significantly decrease motion of the pancreas and diaphragm during treatment.

Repeatability and correlations of dynamic contrast enhanced and T2* MRI in patients with advanced pancreatic ductal adenocarcinoma

BACKGROUND In current oncological practice of pancreatic ductal adenocarcinoma (PDAC), there is a great demand for response predictors and markers for early treatment evaluation. In this study, we investigated the repeatability and the interaction of dynamic contrast enhanced (DCE) and T2* MRI in patients with advanced PDAC to enable for such evaluation using these techniques. MATERIALS & METHODS 15 PDAC patients underwent two DCE, T2* and anatomical 3 T MRI sessions before start of treatment. Parametric maps were calculated for the transfer constant (Ktrans), rate constant (kep), extracellular extravascular space (ve) and perfusion fraction (vp). Quantitative R2* (1/T2*) maps were obtained from the multi-echo T2* images. Differences between normal and cancerous pancreas were determined using a Wilcoxon matched pairs test. Repeatability was obtained using Bland-Altman analysis and relations between DCE and T2*/R2* were observed by Spearman correlation and voxel-wise binned plots of tumor voxels. RESULTS PDAC Ktrans (p = 0.007), kep (p < 0.001), vp (p = 0.035) were lower and ve (p < 0.001) was higher compared to normal pancreas. The coefficient of variation between sessions was 21.8% for Ktrans, 9.9% for kep, 19.3% for ve, 18.2% for vp and 18.7% for R2*. Variation between patients ranged from 20.2% for kep to 43.6% for Ktrans. In the tumor both Ktrans (r = 0.56, p = 0.030) and ve (r = 0.54, p = 0.037) showed a positive correlation with T2*. Voxel wise analysis showed a steep increase in R2* for tumor voxels with lower Ktrans and ve. CONCLUSION We showed good repeatability of DCE and T2* related MRI parameters in advanced PDAC patients. Furthermore, we have illustrated the relation of DCE Ktrans and ve with tissue T2* and R2* indicating substantial value of these parameters for detecting tumor hypoxia in future studies. The results from our study pave the way for further response evaluation studies and patient selection based on DCE and T2* parameters.