E.S. Paulson

Comparison of Dynamic Susceptibility-weighted Contrast-enhanced MR Methods: Recommendations for Measuring Relative Cerebral Blood Volume in Brain Tumors

PURPOSE To investigate whether estimates of relative cerebral blood volume (rCBV) in brain tumors, obtained by using dynamic susceptibility-weighted contrast material-enhanced magnetic resonance (MR) imaging vary with choice of data acquisition and postprocessing methods. MATERIALS AND METHODS Four acquisition methods were used to collect data in 22 high-grade glioma patients, with informed written consent under HIPAA-compliant guidelines approved by the institutional review board. During bolus administration of a standard single dose of gadolinium-based contrast agent (0.1 mmol per kilogram of body weight), one of three acquisition methods was used: gradient-echo (GRE) echo-planar imaging (echo time [TE], 30 msec; flip angle, 90 degrees ; n = 10), small-flip-angle GRE echo-planar imaging (TE, 54 msec; flip angle, 35 degrees ; n = 7), or dual-echo GRE spiral-out imaging (TE, 3.3 and 30 msec; flip angle, 72 degrees ; n = 5). Next, GRE echo-planar imaging (TE, 30 msec; flip angle, 90 degrees ; n = 22) was used to collect data during administration of a second dose of contrast agent (0.2 mmol/kg). Subsequently, six methods of analysis were used to calculate rCBV. Mean rCBV values from whole tumor, tumor hot spots, and contralateral brain were normalized to mean rCBV in normal-appearing white matter. RESULTS Friedman two-way analysis of variance and Kruskal-Wallis one-way analysis of variance results indicated that qualitative rCBV values were dependent on acquisition and postprocessing methods for both tumor and contralateral brain. By using the nonparametric Mann-Whitney test, a consistently positive (greater than zero) tumor-contralateral brain rCBV ratio resulted when either the preload-postprocessing correction approach or dual-echo acquisition approach (P < .008 for both methods) was used. CONCLUSION The dependence of tumor rCBV on the choice of acquisition and postprocessing methods is caused by their varying sensitivities to T1 and T2 and/or T2* leakage effects. The preload-correction approach and dual-echo acquisition approach are the most robust choices for the evaluation of brain tumors when the possibility of contrast agent extravasation exists.

The Role of Preload and Leakage Correction in Gadolinium-Based Cerebral Blood Volume Estimation Determined by Comparison with MION as a Criterion Standard

BACKGROUND AND PURPOSE: Contrast extravasation in DSC-MRI potentiates inaccurate and imprecise estimates of glioma rCBV. We tested assertions that preload and postprocessing algorithms minimize this error by comparing Gd-rCBV using permutations of these 2 techniques with criterion standard rCBV using MION, an intravascular agent. MATERIALS AND METHODS: We imaged 7 Fisher rats with 9L gliosarcomas, by using 3T gradient-echo DSC-MRI with MION (2.0 mg Fe/kg) and staged injection of Gd-diethylene triamine pentaacetic acid: a 0.1-mmol/kg bolus provided no preload (P−) data and served as preload (P+) for a subsequent 0.2-mmol/kg bolus. We computed MION-rCBV (steady-state ΔR2*, tumor versus normal brain) and Gd-rCBV ΔR2* [t] integration) without (C−) and with (C+) postprocessing correction, thereby testing 4 correction permutations: P−C−, P−C+, P+C−, and P+C+. We tested whether each permutation reduced bias and variance of the Gd/MION rCBV differences by using generalized estimating equations and Fmax statistics (P < .05 significant). RESULTS: Gd-rCBV progressively better approximated MION-rCBV with increasing leakage correction. There was no statistically significant bias for the mean percentage deviation of Gd-rCBV from MION-rCBV for any correction permutation, but there was significantly reduced variance by using P+C− (22-fold), P−C+ (32-fold), and P+C+ (267-fold) compared with P−C−. P+C+ provided significant additional variance reduction compared with P+C− (12-fold) and P−C+ (8-fold). Linear regression of Gd-rCBV versus MION-rCBV revealed P+C+ to have the closest slope and intercept compared with the ideal, substantially better than P+C−. CONCLUSIONS: Preload and postprocessing correction significantly reduced the variance of Gd-rCBV estimates, and bias reduction approached significance. Postprocessing correction provide significant benefit beyond preload alone.

Comprehensive MRI simulation methodology using a dedicated MRI scanner in radiation oncology for external beam radiation treatment planning

PURPOSE The use of magnetic resonance imaging (MRI) in radiation oncology is expanding rapidly, and more clinics are integrating MRI into their radiation therapy workflows. However, radiation therapy presents a new set of challenges and places additional constraints on MRI compared to diagnostic radiology that, if not properly addressed, can undermine the advantages MRI offers for radiation treatment planning (RTP). The authors introduce here strategies to manage several challenges of using MRI for virtual simulation in external beam RTP. METHODS A total of 810 clinical MRI simulation exams were performed using a dedicated MRI scanner for external beam RTP of brain, breast, cervix, head and neck, liver, pancreas, prostate, and sarcoma cancers. Patients were imaged in treatment position using MRI-optimal immobilization devices. Radiofrequency (RF) coil configurations and scan protocols were optimized based on RTP constraints. Off-resonance and gradient nonlinearity-induced geometric distortions were minimized or corrected prior to using images for RTP. A multidisciplinary MRI simulation guide, along with window width and level presets, was created to standardize use of MR images during RTP. A quality assurance program was implemented to maintain accuracy and repeatability of MRI simulation exams. RESULTS The combination of a large bore scanner, high field strength, and circumferentially wrapped, flexible phased array RF receive coils permitted acquisition of thin slice images with high contrast-to-noise ratio (CNR) and image intensity uniformity, while simultaneously accommodating patient setup and immobilization devices. Postprocessing corrections and alternative acquisition methods were required to reduce or correct off-resonance and gradient nonlinearity induced geometric distortions. CONCLUSIONS The methodology described herein contains practical strategies the authors have implemented through lessons learned performing clinical MRI simulation exams. In their experience, these strategies provide robust, high fidelity, high contrast MR images suitable for external beam RTP.

DYNAMIC MRI ANALYSIS OF TUMOR AND ORGAN MOTION DURING REST AND DEGLUTITION AND MARGIN ASSESSMENT FOR RADIOTHERAPY OF HEAD-AND-NECK CANCER

PURPOSE To quantify swallowing frequency and tumor and normal structure displacements during deglutition using dynamic magnetic resonance imaging (MRI) and to determine planning target volume (PTV) margins to account for resting and deglutition-induced displacements in patients with head-and-neck cancer (HNC). METHODS AND MATERIALS Twenty-two patients with HNC were imaged in the treatment position using dynamic MRI. Sagittal images were acquired. Two-dimensional displacement was analyzed using contours of normal structures and GTV drawn for one swallowing event. Deglutition-induced displacements were quantified based on position change during deglutition relative to preswallow structure location for anterior (A), posterior (P), superior (S), and inferior (I) directions. Additional long-time MRI series were obtained from a subset of 11 patients while they were resting in order to determine swallowing frequency and duration. PTV margins to account for setup error, frequency and duration of deglutition, and resting and deglutition-induced GTV motion were calculated. RESULTS Mean maximum resting displacements ranged from 1.5 to 3.1 mm for combined GTV subsites. Mean maximum swallowing GTV displacement for combined subsites ranged from 4.0 to 11.6 mm. Swallowing was nonperiodic, with a frequency ranging from 0 to 19 swallows over 12.8 min and mean swallow duration of 3.5 s. Based on the average swallowing characteristics in this cohort, the average PTV margins to account for setup error and tumor motion are estimated to be 4.7 mm anteriorly, 4.2 mm posteriorly, 4.7 mm inferiorly, and 6.0 mm superiorly. CONCLUSIONS The measurable mean maximum resting displacement for the GTV indicates that tumor motion occurs even when the patient is not swallowing. Nonuniform margins should be used as a standard PTV margin that accounts for setup error and tumor motion in radiotherapy of HNC unless adaptive radiotherapy with respect to intrafraction tumor motion is performed. The PTV margin can be individualized to a single patients swallowing characteristics or calculated as an average based on the swallowing data from the cohort.

Variability of Target and Normal Structure Delineation Using Multimodality Imaging for Radiation Therapy of Pancreatic Cancer

PURPOSE To explore the potential of multimodality imaging (dynamic contrast-enhanced magnetic resonance imaging [DCE-MRI], apparent diffusion-coefficient diffusion-weighted imaging [ADC-DWI], fluorodeoxyglucose positron emission tomography [FDG-PET], and computed tomography) to define the gross tumor volume (GTV) and organs at risk in radiation therapy planning for pancreatic cancer. Delineated volumetric changes of DCE-MRI, ADC-DWI, and FDG-PET were assessed in comparison with the finding on 3-dimensional/4-dimensional CT with and without intravenous contrast, and with pathology specimens for resectable and borderline resectable cases of pancreatic cancer. METHODS AND MATERIALS We studied a total of 19 representative patients, whose DCE-MRI, ADC-DWI, and FDG-PET data were reviewed. Gross tumor volume and tumor burden/active region inside pancreatic head/neck or body were delineated on MRI (denoted GTVDCE, and GTVADC), a standardized uptake value (SUV) of 2.5, 40%SUVmax, and 50%SUVmax on FDG-PET (GTV2.5, GTV40%, and GTV50%). Volumes of the pancreas, duodenum, stomach, liver, and kidneys were contoured according to CT (VCT), T1-weighted MRI (VT1), and T2-weighted MRI (VT2) for 7 patients. RESULTS Significant statistical differences were found between the GTVs from DCE-MRI, ADC-DW, and FDG-PET, with a mean and range of 4.73 (1.00-9.79), 14.52 (3.21-25.49), 22.04 (1.00-45.69), 19.10 (4.84-45.59), and 9.80 (0.32-35.21) cm(3) for GTVDCE, GTVADC, GTV2.5, GTV40%, and GTV50%, respectively. The mean difference and range in the measurements of maximum dimension of tumor on DCE-MRI, ADC-DW, SUV2.5, 40%SUVmax, and 50%SUVmax compared with pathologic specimens were -0.84 (-2.24 to 0.9), 0.41 (-0.15 to 2.3), 0.58 (-1.41 to 3.69), 0.66 (-0.67 to 1.32), and 0.15 (-1.53 to 2.38) cm, respectively. The T1- and T2-based volumes for pancreas, duodenum, stomach, and liver were generally smaller compared with those from CT, except for the kidneys. CONCLUSIONS Differences exists between DCE-, ADC-, and FDG-PET-defined target volumes for RT of pancreatic cancer. Organ at risk volumes based on MRI are generally smaller than those based on CT. Further studies combined with pathologic specimens are required to identify the optimal imaging modality or sequence to define GTV.

The Effect of Pulse Sequence Parameters and Contrast Agent Dose on Percentage Signal Recovery in DSC-MRI: Implications for Clinical Applications

BACKGROUND AND PURPOSE: Both technical and pathophysiologic factors affect PSR in DSC-MR imaging. We aimed to determine how TE, flip angle (α), and contrast dose impact PSR in high-grade gliomas. MATERIALS AND METHODS: We retrospectively computed PSR maps for 22 patients with high-grade gliomas, comparing 3 DSC-MR imaging methods by using single-dose gadodiamide without preload administration: A (n = 7), α = 35°, TE = 54 ms; B (n = 5), α = 72°, TE = 30 ms; C (n = 10), α = 90°, TE = 30 ms. Methods A-C served as preload for subsequent dynamic imaging using method D (method C parameters but with double-dose contrast). We compared first- and second-injection tumor PSR for methods C and D (paired t test) and tumor PSR for both injections grouped by the first-injection acquisition method (3-group nonparametric 1-way ANOVA). We compared PSR in tumor and normal brain for each first- and second-injection method group (paired t test). RESULTS: First-injection PSR in tumor and normal brain differed significantly for methods B (P = .01) and C (P = .05), but not A (P = .71). First-injection tumor PSR increased with T1 weighting with a significant main effect of method groupings (P = .0012), but there was no significant main effect for first-injection normal brain (P = .93), or second-injection tumor (P = .95) or normal brain (P = .13). In patients scanned with methods C and D, first-injection PSR significantly exceeded second-injection PSR for tumor (P = .037) and normal brain (P < .001). CONCLUSIONS: PSR strongly depends on the T1 weighting of DSC-MR imaging, including pulse sequence (TE, α) and contrast agent (dose, preload) parameters, with implications for protocol design and the interpretation and comparison of PSR values across tumor types and imaging centers.

MRI-based IMRT planning for MR-linac: comparison between CT- and MRI-based plans for pancreatic and prostate cancers.

The treatment planning in radiation therapy (RT) can be arranged to combine benefits of computed tomography (CT) and magnetic resonance imaging (MRI) together to maintain dose calculation accuracy and improved target delineation. Our aim is study the dosimetric impact of uniform relative electron density assignment on IMRT treatment planning with additional consideration given to the effect of a 1.5 T transverse magnetic field (TMF) in MR-Linac. A series of intensity modulated RT (IMRT) plans were generated for two representative tumor sites, pancreas and prostate, using CT and MRI datasets. Representative CT-based IMRT plans were generated to assess the impact of different electron density (ED) assignment on plan quality using CT without the presence of a 1.5 T TMF. The relative ED (rED) values used were taken from the ICRU report 46. Four types of rED assignment in the organs at risk (OARs), the planning target volumes (PTV) and in the non-specified tissue (NST) were considered. Dose was recalculated (no optimization) using a Monaco 5.09.07a research planning system employing Monte Carlo calculations with an option to include TMF. To investigate the dosimetric effect of different rED assignment, the dose-volume parameters (DVPs) obtained from these specific rED plans were compared to those obtained from the original plans based on CT. Overall, we found that uniform rED assignment results in differences in DVPs within 3% for the PTV and 5% for OAR. The presence of 1.5 T TMF on IMRT DVPs resulted in differences that were generally within 3% of the Gold St for both the pancreas and prostate. The combination of uniform rED assignment and TMF produced differences in DVPs that were within 4-5% of the Gold St. Larger differences in DVPs were observed for OARs on T2-based plans. The effects of using different rED assignments and the presence of 1.5 T TMF for pancreas and prostate IMRT plans are generally within 3% and 5% of PTV and OAR Gold St values. There are noticeable dosimetric differences between the CT- and MRI-based IMRT plans caused by a combination of anatomical changes between the two image acquisition times, uniform rED assignment and 1.5 T TMF.

Consensus opinion on MRI simulation for external beam radiation treatment planning

AIM To determine the levels at which consensus could be reached regarding general and site-specific principles of MRI simulation for offline MRI-aided external beam radiation treatment planning. METHODS A process inspired by the Delphi method was employed to determine levels of consensus using a series of questionnaires interspersed with controlled opinion feedback. RESULTS In general, full consensus was reached regarding general principles of MRI simulation. However, the level of consensus decreased when site-specific principles of MRI simulation were considered. CONCLUSIONS These results indicate variability in MRI simulation approaches that are largely explained by the use of MRI in combination with CT.

Internal margin assessment using cine MRI analysis of deglutition in head and neck cancer radiotherapy

PURPOSE Intensity-modulated radiation therapy (IMRT) is a promising treatment modality for patients with head and neck cancer (HNC). The dose distributions from IMRT are static and, thus, are unable to account for variations and/or uncertainties in the relationship between the patient (region being treated) and the beam. Organ motion comprises one such source of this uncertainty, introduced by physiological variation in the position, size, and shape of organs during treatment. In the head and neck, the predominant source of this variation arises from deglutition (swallowing). The purpose of this study was to investigate whether cinematographic MRI (cine MRI) could be used to determine asymmetric (nonuniform) internal margin (IM) components of tumor planning target volumes based on the actual deglutition-induced tumor displacement. METHODS Five head and neck cancer patients were set up in treatment position on a 3 T MRI scanner. Two time series of single-slice, sagittal, cine images were acquired using a 2D FLASH sequence. The first time series was a 12.8 min scan designed to capture the frequency and duration of deglutition in the treatment position. The second time series was a short, 15 s scan designed to capture the displacement of deglutition in the treatment position. Deglutition frequency and mean swallow duration were estimated from the long time series acquisition. Swallowing and resting (nonswallowing) events were identified on the short time series acquisition and displacement was estimated based on contours of gross tumor volume (GTV) generated at each time point of a particular event. A simple linear relationship was derived to estimate 1D asymmetric IMs in the presence of resting- and deglutition-induced displacement. RESULTS Deglutition was nonperiodic, with frequency and duration ranging from 2.89-24.18 mHz and from 3.86 to 6.10 s, respectively. The deglutition frequency and mean duration were found to vary among patients. Deglutition-induced maximal GTV displacements ranged from 0.00 to 28.36 mm with mean and standard deviation of 4.72 +/- 3.18, 3.70 +/- 2.81, 2.75 +/- 5.24, and 10.40 +/- 10.76 mm in the A, P, I, and S directions, respectively. Resting-induced maximal GTV displacement ranged from 0.00 to 5.59 mm with mean and standard deviation of 3.01 +/- 1.80, 1.25 +/- 1.10, 3.23 +/- 2.20, and 2.47 +/- 1.11 mm in the A, P, I, and S directions, respectively. For both resting and swallowing states, displacement along the S-I direction dominated displacement along the A-P direction. The calculated IMs were dependent on deglutition frequency, ranging from 3.28-4.37 mm for the lowest deglutition frequency patient to 3.76-6.43 mm for the highest deglutition frequency patient. A statistically significant difference was detected between IMs calculated for P and S directions (p = 0.0018). CONCLUSIONS Cine MRI is able to capture tumor motion during deglutition. Swallowing events can be demarcated by MR signal intensity changes caused by anatomy containing fully relaxed spins that move medially into the imaging plane during deglutition. Deglutition is nonperiodic and results in dynamic changes in the tumor position. Deglutition-induced displacements are larger and more variable than resting displacements. The nonzero mean maximum resting displacement indicates that some tumor motion occurs even when the patient is not swallowing. Asymmetric IMs, derived from deglutition frequency, duration, and directional displacement, should be employed to account for tumor motion in HNC RT.

Investigation of undersampling and reconstruction algorithm dependence on respiratory correlated 4D-MRI for online MR-guided radiation therapy

The purpose of this work is to investigate the effects of undersampling and reconstruction algorithm on the total processing time and image quality of respiratory phase-resolved 4D MRI data. Specifically, the goal is to obtain quality 4D-MRI data with a combined acquisition and reconstruction time of five minutes or less, which we reasoned would be satisfactory for pre-treatment 4D-MRI in online MRI-gRT. A 3D stack-of-stars, self-navigated, 4D-MRI acquisition was used to scan three healthy volunteers at three image resolutions and two scan durations. The NUFFT, CG-SENSE, SPIRiT, and XD-GRASP reconstruction algorithms were used to reconstruct each dataset on a high performance reconstruction computer. The overall image quality, reconstruction time, artifact prevalence, and motion estimates were compared. The CG-SENSE and XD-GRASP reconstructions provided superior image quality over the other algorithms. The combination of a 3D SoS sequence and parallelized reconstruction algorithms using computing hardware more advanced than those typically seen on product MRI scanners, can result in acquisition and reconstruction of high quality respiratory correlated 4D-MRI images in less than five minutes.