Magnetic resonance coherence pathway unraveling.

Efficiently acquiring multi-contrast magnetic resonance imaging data is crucial for patient comfort and clinical throughput. Developing scan acceleration methods tailored for specific applications drastically improves the value of an MRI examination. Here, we propose a novel method to control the aliasing of simultaneously acquired images of multiple spin echo coherence pathways with the goal of producing high quality multi-contrast images from a single acquisition. Modulating the radiofrequency phase of several pulses applied in brief succession also uniquely modulates the phase of spin echo coherence pathways. A method, termed magnetic resonance coherence pathway unraveling (MR-CPU), to control the aliasing of simultaneously acquired coherence pathway images is developed here along with parallel imaging-based reconstruction methods to separate them. MR-CPU was validated in phantom experiments and tested in vivo. High levels of correlation between reference pathway images and MR-CPU-derived coherence pathway images were found from the phantom experiments. Minimal artifacts arising from the separation of the overlapped coherence pathway images were observed in vivo. MR-CPU provides a novel mechanism through which to acquire and separate multiple overlapped coherence pathway images, thus adding to the diagnostic potential of an MRI exam without the penalty of additional scan time.

Low-rank inversion reconstruction for through-plane accelerated radial MR fingerprinting applied to relaxometry at 0.35 T.

PURPOSE: To reduce scan time, methods to accelerate phase-encoded/non-Cartesian MR fingerprinting (MRF) acquisitions for variable density spiral acquisitions have recently been developed. These methods are not applicable to MRF acquisitions, wherein a single k-space spoke is acquired per frame. Therefore, we propose a low-rank inversion method to resolve MRF contrast dynamics from through-plane accelerated Cartesian/radial measurements applied to quantitative relaxation-time mapping on a 0.35T system. METHODS: An algorithm was implemented to reconstruct through-plane aliased low-rank images describing the contrast dynamics occurring because of the transient-state MRF acquisition. T1 and T2 times from accelerated acquisitions were compared with those from unaccelerated linear reconstructions in a standardized system phantom and within in vivo brain and prostate experiments on a hybrid 0.35T MRI/linear accelerator. RESULTS: No significant differences between T1 and T2 times for the accelerated reconstructions were observed compared to fully sampled acquisitions (p = 0.41 and p = 0.36, respectively). The mean absolute errors in T1 and T2 were 5.6% and 2.9%, respectively, between the full and accelerated acquisitions. The SDs in T1 and T2 decreased with the advanced accelerated reconstruction compared with the unaccelerated reconstruction (p = 0.02 and p = 0.03, respectively). The quality of the T1 and T2 maps generated with the proposed approach are comparable to those obtained using the unaccelerated data sets. CONCLUSIONS: Through-plane accelerated MRF with radial k-space coverage was demonstrated at a low field strength of 0.35 T. This method enabled 3D T1 and T2 mapping at 0.35 T with a 3-min scan.

Toward magnetic resonance fingerprinting for low-field MR-guided radiation therapy.

PURPOSE: The acquisition of multiparametric quantitative magnetic resonance imaging (qMRI) is becoming increasingly important for functional characterization of cancer prior to- and throughout the course of radiation therapy. The feasibility of a qMRI method known as magnetic resonance fingerprinting (MRF) for rapid T1 and T2 mapping was assessed on a low-field MR-linac system. METHODS: A three-dimensional MRF sequence was implemented on a 0.35T MR-guided radiotherapy system. MRF-derived measurements of T1 and T2 were compared to those obtained with gold standard single spin echo methods, and the impacts of the radiofrequency field homogeneity and scan times ranging between 6 and 48 min were analyzed by acquiring between 1 and 8 spokes per time point in a standard quantitative system phantom. The short-term repeatability of MRF was assessed over three measurements taken over a 10-h period. To evaluate transferability, MRF measurements were acquired on two additional MR-guided radiotherapy systems. Preliminary human volunteer studies were performed. RESULTS: The phantom benchmarking studies showed that MRF is capable of mapping T1 and T2 values within 8% and 10% of gold standard measures, respectively, at 0.35T. The coefficient of variation of T1 and T2 estimates over three repeated scans was < 5% over a broad range of relaxation times. The T1 and T2 times derived using a single-spoke MRF acquisition across three scanners were near unity and mean percent errors in T1 and T2 estimates using the same phantom were < 3%. The mean percent differences in T1 and T2 as a result of truncating the scan time to 6 min over the large range of relaxation times in the system phantom were 0.65% and 4.05%, respectively. CONCLUSIONS: The technical feasibility and accuracy of MRF on a low-field MR-guided radiation therapy device has been demonstrated. MRF can be used to measure accurate T1 and T2 maps in three dimensions from a brief 6-min scan, offering strong potential for efficient and reproducible qMRI for future clinical trials in functional plan adaptation and tumor/normal tissue response assessment.

On the use of low-dimensional temporal subspace constraints to reduce reconstruction time and improve image quality of accelerated 4D-MRI.

BACKGROUND AND PURPOSE: The purpose of this work is to investigate the use of low-dimensional temporal subspace constraints for 4D-MRI reconstruction from accelerated data in the context of MR-guided online adaptive radiation therapy (MRgOART). MATERIALS AND METHODS: Subspace basis functions are derived directly from the accelerated golden angle radial stack-of-stars 4D-MRI data. The reconstruction times, image quality, and motion estimates are investigated as a function of the number of subspace coefficients and compared with a conventional frame-by-frame reconstruction. These experiments were performed in five patients with four 4D-MRI scans per patient on a 1.5T MR-Linac. RESULTS: If two or three subspace coefficients are used, the iterative reconstruction time is reduced by 32% and 18%, respectively, compared to conventional parallel imaging with compressed sensing reconstructions. No significant difference was found between motion estimates made with the subspace-constrained reconstructions (p > 0.08). Qualitative improvements in image quality included reduction in apparent noise and reductions in streaking artifacts from the radial k-space coverage. CONCLUSION: Incorporating subspace constraints for accelerated 4D-MRI reconstruction reduces noise and residual undersampling artifacts in the images while reducing computation time, making it a strong candidate for use in clinical MRgOART workflows.

Split-slice training and hyperparameter tuning of RAKI networks for simultaneous multi-slice reconstruction.

PURPOSE: Simultaneous multi-slice acquisitions are essential for modern neuroimaging research, enabling high temporal resolution functional and high-resolution q-space sampling diffusion acquisitions. Recently, deep learning reconstruction techniques have been introduced for unaliasing these accelerated acquisitions, and robust artificial-neural-networks for k-space interpolation (RAKI) have shown promising capabilities. This study systematically examines the impacts of hyperparameter selections for RAKI networks, and introduces a novel technique for training data generation which is analogous to the split-slice formalism used in slice-GRAPPA. METHODS: RAKI networks were developed with variable hyperparameters and with and without split-slice training data generation. Each network was trained and applied to five different datasets including acquisitions harmonized with Human Connectome Project lifespan protocol. Unaliasing performance was assessed through L1 errors computed between unaliased and calibration frequency-space data. RESULTS: Split-slice training significantly improved network performance in nearly all hyperparameter configurations. Best unaliasing results were achieved with three layer RAKI networks using at least 64 convolutional filters with receptive fields of 7 voxels, 128 single-voxel filters in the penultimate RAKI layer, batch normalization, and no training dropout with the split-slice augmented training dataset. Networks trained without the split-slice technique showed symptoms of network over-fitting. CONCLUSIONS: Split-slice training for simultaneous multi-slice RAKI networks positively impacts network performance. Hyperparameter tuning of such reconstruction networks can lead to further improvements in unaliasing performance.

A Patient-Specific Autosegmentation Strategy Using Multi-Input Deformable Image Registration for Magnetic Resonance Imaging-Guided Online Adaptive Radiation Therapy: A Feasibility Study.

PURPOSE: Magnetic resonance-guided online adaptive radiation therapy (MRgOART) requires accurate and efficient segmentation. However, the performance of current autosegmentation tools is generally poor for magnetic resonance imaging (MRI) owing to day-to-day variations in image intensity and patient anatomy. In this study, we propose a patient-specific autosegmentation strategy using multiple-input deformable image registration (DIR; PASSMID) to improve segmentation accuracy and efficiency for MRgOART. METHODS AND MATERIALS: Longitudinal MRI scans acquired on a 1.5T MRI-Linac for 10 patients with abdominal cancer were used. The proposed PASSMID includes 2 steps: applying a patient-specific image processing pipeline to longitudinal MRI scans, and populating all contours from previous sessions/fractions to a new fractional MRI using multiple DIRs and combining the resulted contours using simultaneous truth and performance level estimation (STAPLE) to obtain the final consensus segmentation. Five contour propagation strategies were compared: planning computed tomography to fractional MRI scans through rigid body registration (RDR), pretreatment MRI to fractional MRI scans through RDR and DIR, and the proposed multi-input DIR/STAPLE without preprocessing, and the PASSMID. Dice similarity coefficient (DSC) and mean distance to agreement (MDA) with ground truth contours were calculated slice by slice to quantify the contour accuracy. A quantitative index, defined as the ratio of acceptable slices, was introduced using a criterion of DSC > 0.8 and MDA < 2 mm. RESULTS: The proposed PASSMID performed well with an average 2-dimensional DSC/MDA of 0.94/1.78 mm, 0.93/1.04 mm, 0.93/1.06 mm, 0.93/1.14 mm, 0.92/0.83 mm, 0.84/1.53 mm, 0.86/2.39 mm, 0.81/2.49 mm, 0.72/5.48 mm, and 0.70/5.03 mm for the liver, left kidney, right kidney, spleen, aorta, pancreas, stomach, duodenum, small bowel, and colon, respectively. Starting from the third fractions, the contour accuracy was significantly improved with PASSMID compared with the single-DIR strategy (P < .05). The mean ratio of acceptable slices were 13.9%, 17.5%, 60.8%, 70.6%, and 71.8% for the 5 strategies, respectively. CONCLUSIONS: The proposed PASSMID solution, by combining image processing, multi-input DIRs, and STAPLE, can significantly improve the accuracy of autosegmentation for intrapatient MRI scans, reducing the time required for further contour editing, thereby facilitating the routine practice of MRgOART.

Initial clinical experience of Stereotactic Body Radiation Therapy (SBRT) for liver metastases, primary liver malignancy, and pancreatic cancer with 4D-MRI based online adaptation and real-time MRI monitoring using a 1.5 Tesla MR-Linac.

PURPOSE/OBJECTIVES: Recently a 1.5 Tesla MR Linac has been FDA approved and is commercially available. Clinical series describing treatment methods and outcomes for upper abdominal tumors using a 1.5 Tesla MR Linac are lacking. We present the first clinical series of upper abdominal tumors treated using a 1.5 Tesla MR Linac along with the acquisition of intra-treatment quantitative imaging. MATERIALS/METHODS: 10 patients with abdominal tumors were treated at our institution. Each patient enrolled in an IRB approved advanced imaging protocol. Both daily real-time adaptive and non-adaptive methods were used, and selection criteria are described. Adaptive plans were based on pre-beam motion-averaged or mid-position images derived from respiratory-correlated 4D-MRI. Quantitative intravoxel incoherent motion diffusion-weighted imaging and T2 mapping were acquired during plan adaptation. Real-time motion monitoring using cine MRI was performed during beam-on. RESULTS: Median patient age was 68.2, five patients were female. Tumor types included liver metastatic lesions from melanoma and sarcoma, primary liver hepatocellular carcinoma (HCC), and regional abdominal tumors included pancreatic metastatic lesions from renal cell carcinoma (RCC) along with two cases of recurrent pancreatic cancer. Doses included 30 Gy in 6 fractions, 33 Gy in 5 fractions, 50 Gy in 5 fractions, 45 Gy in 3 fractions, and 60 Gy in 3 fractions, depending on the location and clinical circumstances. Treatments were feasible and were successfully completed in all patients without significant acute toxicity, technical complications, or need for back up CT based treatment plans. CONCLUSIONS: We present a first clinical series of patients treated for pancreatic tumors, primary liver tumors, and secondary liver tumors with a 1.5 Tesla MR Linear accelerator using adapt-to-position and adapt-to-shape strategies. Treatments were well tolerated by all patients. Acquisition of fully quantitative MR imaging was feasible during the course of the treatment delivery workflow without extending overall treatment times.

4D-MRI driven MR-guided online adaptive radiotherapy for abdominal stereotactic body radiation therapy on a high field MR-Linac: Implementation and initial clinical experience.

BACKGROUND AND PURPOSE: In this report, we describe our implementation and initial clinical experience using 4D-MRI driven MR-guided online adaptive radiotherapy (MRgOART) for abdominal stereotactic body radiotherapy (SBRT) on the Elekta Unity MR-Linac. MATERIALS AND METHODS: Eleven patients with abdominal malignancies were treated with free-breathing SBRT in three to five fractions on a 1.5 T MR-Linac. Online adaptive plans were generated using Adapt-To-Position (ATP) or Adapt-To-Shape (ATS) workflows based on motion averaged or mid-position images derived from a pre-beam 4D-MRI. A high performance server positioned on the local MR-Linac machine network was utilized for 4D-MR image reconstruction. A parallel contour editing approach was employed in the ATS workflow. Intravoxel incoherent motion (IVIM) and T2 mapping sequences were acquired during adaptive planning in both ATP and ATS workflows for treatment response monitoring. Adaptive plans were delivered under real-time cine image motion monitoring. RESULTS: The shortest 4D-MRI time-to-image was the motion averaged image, followed by mid position and respiratory binned images. In this cohert of patients, 50% of treatments utilized the ATS workflow; the remaining treatments utilized the ATP workflow. Mid-position images were utilized as daily planning images for two of the eleven patients. The mean daily adaptive plan secondary dose calculation and ArcCheck 3D Gamma passing rates were 97.5% (92.1-100.0%) and 99.3% (96.2-100.0%), respectively. The median overall treatment times for abdominal SBRT was 46 and 62 min for ATP and ATS workflows, respectively. CONCLUSION: We have successfully implemented and utilized a 4D-MRI driven MRgOART process with ATP and ATS workflows for free-breathing abdominal SBRT on a 1.5 T Elekta Unity MR-Linac.

Generalized simultaneous multi-orientation 2D imaging.

PURPOSE: Flexibility in slice prescription is critical for precise motion monitoring during MR-guided therapies. Adding more slices to improve spatial coverage during rapid 2D cine imaging often hampers temporal resolution. This work describes a framework to simultaneously acquire multiple arbitrarily oriented slices which share a common frequency encoding axis. This framework allows for higher frame rates for a given number of slices compared to conventional interleaved-slice multi-orientation cine imaging. THEORY AND METHODS: A framework to calculate zeroth gradient moments to be played out between sequentially excited slices with multiple orientations is described here. Experiments were performed in phantom, and in vivo in the head/neck and abdomen of patients. RESULTS: Images arbitrarily rotated relative to one another were successfully obtained in phantom and in vivo. Simultaneous multi-orientation (SMO) images were also acquired with additional in-plane acceleration to demonstrate the capability of this method to rapidly image objects moving with physiological motion. CONCLUSIONS: The technical feasibility of the generalized SMO imaging framework was tested in this study. It shows promise for continued development for motion monitoring during MR-guided therapies.

Simultaneous acquisition of orthogonal plane cine imaging and isotropic 4D-MRI using super-resolution.

INTRODUCTION: Effective management of intrafraction motion is critical to the success of MR-guided radiation therapy (MR-gRT) of abdominal or thoracic tumors. Recent developments have proposed the use of cine MRI to monitor motion and 4D-MRI to aid in the reconstruction of dose actually delivered to patients. The present work aims to develop and perform preliminary testing of an imaging framework capable of simultaneously acquiring orthogonal plane cine imaging and isotropic resolution 4D-MRI volumes using super-resolution methods. METHODS: A pulse sequence was developed to acquire time-locked cine imaging in sagittal and coronal planes while additionally acquiring 4D-MRIs in both planes simultaneously. Isotropic resolution 4D-MRIs were reconstructed by combining information from the orthogonal volumes using super-resolution methods. This method was tested in phantoms and in liver cancer patients. RESULTS: Simultaneous cine imaging in sagittal and coronal planes allowed monitoring of respiratory motion and an accurate binning of concurrently acquired 4D imaging slices into the appropriate respiratory phases. The super-resolution reconstruction methods improved the resolution of the 4D-MRI along both of the low-resolution slice-select dimensions. CONCLUSIONS: The development and preliminary testing of an imaging framework capable of acquiring simultaneous orthogonal cine imaging and super-resolution 4D-MRI was performed. The promising results merit further investigation for use in dose reconstruction during MR-guided radiation therapy.

Simultaneous motion monitoring and truth-in-delivery analysis imaging framework for MR-guided radiotherapy.

Intrafraction motion (i.e. motion occurring during a treatment session) can play a pivotal role in the success of abdominal and thoracic radiation therapy. Hybrid magnetic resonance-guided radiotherapy (MR-gRT) systems have the potential to control for intrafraction motion. Recently, we introduced an MRI sequence capable of acquiring real-time cine imaging in two orthogonal planes (SOPI). We extend SOPI here to permit dynamic updating of slice positions in one-plane while keeping the other plane position fixed. In this implementation, cine images from the static plane are used for motion monitoring and as image navigators to sort stepped images in the other plane, producing dynamic 4D image volumes for use in dose reconstruction. A custom 3D-printed target, designed to mimic the pancreas and duodenum and filled with radiochromic FXG gel, was interfaced to the dynamic motion phantom. 4D-SOPI was acquired in a dynamic motion phantom driven by an actual patient respiratory waveform displaying amplitude/frequency variations and drifting and in a healthy volunteer. Unique 4D-MRI epochs were reconstructed from a time series of phantom motion. Dose from a static 4 cm × 15 cm field was calculated on each 4D respiratory phase bin and epoch image, scaled by the time spent in each bin, and then rigidly accumulated. The phantom was then positioned on an Elekta MR-Linac and irradiated while moving. Following irradiation, actual dose deposited to the FXG gel was determined by applying a R 1 versus dose calibration curve to R 1 maps of the phantom. The 4D-SOPI cine images produced a respiratory motion navigator that was highly correlated with the actual phantom motion (CC = 0.9981). The mean difference between the accumulated and measured dose inside the target was 4.4% of the maximum prescribed dose. These initial results demonstrate that 4D-SOPI is a promising imaging framework enabling simultaneous real-time motion monitoring and truth-in-delivery analysis for integrated MR-gRT systems.

Simultaneous orthogonal plane cine imaging with balanced steady-state free-precession contrast using k-t GRAPPA.

The goal of this study is to present a framework that allows cine images in orthogonal planes to be reconstructed simultaneously using slice-interleaved acquisitions and k-t GRAPPA. Slice-interleaved acquisitions can be interpreted as an undersampled k-t space in which data are desired at skipped frames. Local spatiotemporal correlations can be exploited to interpolate the skipped data to reconstruct images in orthogonal slice groups simultaneously. An in vivo experiment was performed in which interleaved sagittal and coronal balanced steady-state free-precession data were acquired in the abdomens of volunteers breathing normally. k-t GRAPPA weights were calculated from separate calibration scans and applied to the slice-interleaved data. The images from the interpolated frames have a similar contrast to the acquired frames, and the use of k-t GRAPPA improved the anatomical alignment between the orthogonal images in the presence of motion. The k-t GRAPPA reconstruction of slice-interleaved data is a promising method for obtaining cine images of orthogonal slices simultaneously with arbitrary contrast.

Particle Filter-Based Target Tracking Algorithm for Magnetic Resonance-Guided Respiratory Compensation: Robustness and Accuracy Assessment.

PURPOSE: To assess overall robustness and accuracy of a modified particle filter-based tracking algorithm for magnetic resonance (MR)-guided radiation therapy treatments. METHODS AND MATERIALS: An improved particle filter-based tracking algorithm was implemented, which used a normalized cross-correlation function as the likelihood calculation. With a total of 5 healthy volunteers and 8 patients, the robustness of the algorithm was tested on 24 dynamic magnetic resonance imaging (MRI) time series with varying resolution, contrast, and signal-to-noise ratio. The complete data set included data acquired with different scan parameters on a number of MRI scanners with varying field strengths, including the 1.5T MR linear accelerator. Tracking errors were computed by comparing the results obtained by the particle filter algorithm with experts' delineations. RESULTS: The ameliorated tracking algorithm was able to accurately track abdominal as well as thoracic tumors, whereas the previous Bhattacharyya distance-based implementation failed in more than 50% of the cases. The tracking error, combined over all MRI acquisitions, is 1.1 ± 0.4 mm, which demonstrated high robustness against variations in contrast, noise, and image resolution. Finally, the effect of the input/control parameters of the model was very similar across all cases, suggesting a class-based optimization is possible. CONCLUSIONS: The modified particle filter tracking algorithm is highly accurate and robust against varying image quality. This makes the algorithm a promising candidate for automated tracking on the MR linear accelerator.

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.

Simultaneous orthogonal plane imaging.

PURPOSE: Intrafraction motion can result in a smearing of planned external beam radiation therapy dose distributions, resulting in an uncertainty in dose actually deposited in tissue. The purpose of this paper is to present a pulse sequence that is capable of imaging a moving target at a high frame rate in two orthogonal planes simultaneously for MR-guided radiotherapy. THEORY: By balancing the zero gradient moment on all axes, slices in two orthogonal planes may be spatially encoded simultaneously. The orthogonal slice groups may be acquired with equal or nonequal echo times. METHODS: A Cartesian spoiled gradient echo simultaneous orthogonal plane imaging (SOPI) sequence was tested in phantom and in vivo. Multiplexed SOPI acquisitions were performed in which two parallel slices were imaged along two orthogonal axes simultaneously. An autocalibrating phase-constrained 2D-SENSE-GRAPPA (generalized autocalibrating partially parallel acquisition) algorithm was implemented to reconstruct the multiplexed data. RESULTS: SOPI images without intraslice motion artifacts were reconstructed at a maximum frame rate of 8.16 Hz. The 2D-SENSE-GRAPPA reconstruction separated the parallel slices aliased along each orthogonal axis. CONCLUSION: The high spatiotemporal resolution provided by SOPI has the potential to be beneficial for intrafraction motion management during MR-guided radiation therapy or other MRI-guided interventions. Magn Reson Med 78:1700-1710, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Wavelet Domain Radiofrequency Pulse Design Applied to Magnetic Resonance Imaging.

A new method for designing radiofrequency (RF) pulses with numerical optimization in the wavelet domain is presented. Numerical optimization may yield solutions that might otherwise have not been discovered with analytic techniques alone. Further, processing in the wavelet domain reduces the number of unknowns through compression properties inherent in wavelet transforms, providing a more tractable optimization problem. This algorithm is demonstrated with simultaneous multi-slice (SMS) spin echo refocusing pulses because reduced peak RF power is necessary for SMS diffusion imaging with high acceleration factors. An iterative, nonlinear, constrained numerical minimization algorithm was developed to generate an optimized RF pulse waveform. Wavelet domain coefficients were modulated while iteratively running a Bloch equation simulator to generate the intermediate slice profile of the net magnetization. The algorithm minimizes the L2-norm of the slice profile with additional terms to penalize rejection band ripple and maximize the net transverse magnetization across each slice. Simulations and human brain imaging were used to demonstrate a new RF pulse design that yields an optimized slice profile and reduced peak energy deposition when applied to a multiband single-shot echo planar diffusion acquisition. This method may be used to optimize factors such as magnitude and phase spectral profiles and peak RF pulse power for multiband simultaneous multi-slice (SMS) acquisitions. Wavelet-based RF pulse optimization provides a useful design method to achieve a pulse waveform with beneficial amplitude reduction while preserving appropriate magnetization response for magnetic resonance imaging.

Location of brain tumor intersecting white matter tracts predicts patient prognosis.

Brain tumor cells invade adjacent normal brain along white matter (WM) bundles of axons. We therefore hypothesized that the location of tumor intersecting WM tracts would be associated with differing survival. This study introduces a method, voxel-wise survival analysis (VSA), to determine the relationship between the location of brain tumor intersecting WM tracts and patient prognosis. 113 primary glioblastoma (GBM) patients were retrospectively analyzed for this study. Patient specific tumor location, defined by contrast-enhancement, was combined with diffusion tensor imaging derived tractography to determine the location of axons intersecting tumor enhancement (AXITEs). VSA was then used to determine the relationship between the AXITE location and patient survival. Tumors intersecting the right anterior thalamic radiation (ATR), right inferior fronto-occipital fasciculus (IFOF), right and left cortico-spinal tract (CST), and corpus callosum (CC) were associated with decreased overall survival. Tumors intersecting the CST, body of the CC, right ATR, posterior IFOF, and inferior longitudinal fasciculus are associated with decreased progression-free survival (PFS), while tumors intersecting the right genu of the CC and anterior IFOF are associated with increased PFS. Patients with tumors intersecting the ATR, IFOF, CST, or CC had significantly improved survival prognosis if they were additionally treated with bevacizumab. This study demonstrates the usefulness of VSA by locating AXITEs associated with poor prognosis in GBM patients. This information should be included in patient-physician conversations, therapeutic strategy, and clinical trial design.

Precise ex vivo histological validation of heightened cellularity and diffusion-restricted necrosis in regions of dark apparent diffusion coefficient in 7 cases of high-grade glioma.

BACKGROUND: Recent conflicting reports have found both brain tumor hypercellularity and necrosis in regions of restricted diffusion on MRI-derived apparent diffusion coefficient (ADC) images. This study precisely compares ADC and cell density voxel by voxel using postmortem human whole brain samples. METHODS: Patients with meningioma were evaluated to determine a normative ADC distribution within benign fluid attenuated inversion recovery (FLAIR) T2/hyperintensity surrounding tumor. This distribution was used to calculate a minimum ADC threshold to define regions of ADC-FLAIR mismatch (AFMM), where restricted diffusion presented in conjunction with T2/FLAIR hyperintensity. Contrast-enhancing voxels were excluded from this analysis. AFMM maps were generated using imaging acquired prior to death in 7 patients with high-grade glioma who eventually donated their brains upon death. Histological samples were taken from numerous regions of abnormal FLAIR and AFMM. Each sample was computationally processed to determine cell density. Custom software was then used to downsample coregistered microscopic histology to the more coarse MRI resolution. A voxel-by-voxel evaluation comparing ADC and cellularity was then performed. RESULTS: An ADC threshold of 0.929 × 10(-3) mm(2)/s was calculated from meningioma-induced edema and was used to define AFMM. Regions of AFMM showed significantly greater cell density in 6 of 7 high-grade glioma cases compared with regions of hyperintense FLAIR alone (P < .0001). Two patients had small regions of diffusion-restricted necrosis that had significantly lower ADC than nearby hypercellularity. CONCLUSIONS: Regions of AFMM contain hypercellularity except for regions with extremely restricted diffusion, where necrosis is present.