INVESTIGATING THE METABOLIC PROGRESSION OF GLIOBLASTOMA WITH HYPERPOLARIZED MAGNETIC RESONANCE

Rapid diagnosis and therapeutic monitoring of aggressive diseases such as glioblastoma (GBM) can improve patient survival by providing physicians the time to optimally deliver treatment. This includes early in development, while the tumor is still manageable, or following initial therapy, when alternative treatments should be considered. The main goal of this project was to determine whether metabolic imaging with hyperpolarized magnetic resonance spectroscopy (MRS) could detect changes in tumor progression more rapidly than conventional anatomic magnetic resonance imaging (MRI) in patient-derived GBM murine models. To comprehensively capture the dynamic nature of cancer metabolism, in vivo pyruvate-to-lactate conversion with hyperpolarized MRI, ex vivo metabolite pool size with nuclear magnetic resonance (NMR) spectroscopy, and ex vivo protein expression with immunohistochemistry (IHC) were measured at several time-points throughout tumor progression (tumor development, regression, and recurrence). Hyperpolarized MRS was capable of detecting significant changes in pyruvate-to-lactate conversion throughout tumor progression, whereas tumor volume measured with anatomic MRI was not significantly altered during regression or recurrence. This was accompanied by alterations in amino acid and phospholipid lipid metabolism and MCT1 expression. It is discussed how hyperpolarized MRS can help address clinical challenges such as identifying malignant disease prior to aggressive growth, differentiating pseudoprogression from true progression, quantifying treatment response, and predicting relapse. The individual evolution of these metabolic assays as well as their correlations with one another provides context for further academic research. In addition to investigating GBM tumor progression, preliminary and supporting metabolic profiling data acquired with NMR spectroscopy is presented in the context of immunometabolism. Specifically, metabolic events associated with the licensing process of natural killer cells as well as macrophage polarization are analyzed. Collectively, this work demonstrates the value of interrogating the metabolism of GBM and tumor-associated immune cells with hyperpolarized MRS and NMR spectroscopy

Assessment and comparison of physician-reported staging using the AJCC staging system in Head and Neck Cancer

https://openworks.mdanderson.org/sumexp21/1183/thumbnail.jp

Intensity standardization methods in magnetic resonance imaging of head and neck cancer

BACKGROUND AND PURPOSE: Conventional magnetic resonance imaging (MRI) poses challenges in quantitative analysis because voxel intensity values lack physical meaning. While intensity standardization methods exist, their effects on head and neck MRI have not been investigated. We developed a workflow based on healthy tissue region of interest (ROI) analysis to determine intensity consistency within a patient cohort. Through this workflow, we systematically evaluated intensity standardization methods for MRI of head and neck cancer (HNC) patients.MATERIALS AND METHODS: Two HNC cohorts (30 patients total) were retrospectively analyzed. One cohort was imaged with heterogenous acquisition parameters (HET cohort), whereas the other was imaged with homogenous acquisition parameters (HOM cohort). The standard deviation of cohort-level normalized mean intensity (SD NMI c), a metric of intensity consistency, was calculated across ROIs to determine the effect of five intensity standardization methods on T2-weighted images. For each cohort, a Friedman test followed by a post-hoc Bonferroni-corrected Wilcoxon signed-rank test was conducted to compare SD NMI c among methods. RESULTS: Consistency (SD NMI c across ROIs) between unstandardized images was substantially more impaired in the HET cohort (0.29 ± 0.08) than in the HOM cohort (0.15 ± 0.03). Consequently, corrected p-values for intensity standardization methods with lower SD NMI c compared to unstandardized images were significant in the HET cohort (p &lt; 0.05) but not significant in the HOM cohort (p &gt; 0.05). In both cohorts, differences between methods were often minimal and nonsignificant. CONCLUSIONS: Our findings stress the importance of intensity standardization, either through the utilization of uniform acquisition parameters or specific intensity standardization methods, and the need for testing intensity consistency before performing quantitative analysis of HNC MRI.</p

Prospective Evaluation of In Vivo and Phantom Repeatability and Reproducibility of Diffusion-Weighted MRI Sequences on 1.5T MRI-Linear Accelerator (MR-Linac) and MR Simulator Devices for Head and Neck Cancers

INTRODUCTION: Diffusion-weighted imaging (DWI) on MRI-linear accelerator (MR-linac) systems can potentially be used for monitoring treatment response and adaptive radiotherapy in head and neck cancers (HNC) but requires extensive validation. We performed technical validation to compare six total DWI sequences on an MR-linac and MR simulator (MR sim) in patients, volunteers, and phantoms. METHODS: Ten human papillomavirus-positive oropharyngeal cancer patients and ten healthy volunteers underwent DWI on a 1.5T MR-linac with three DWI sequences: echo planar imaging (EPI), split acquisition of fast spin echo signals (SPLICE), and turbo spin echo (TSE). Volunteers were also imaged on a 1.5T MR sim with three sequences: EPI, BLADE (vendor tradename), and readout segmentation of long variable echo trains (RESOLVE). Participants underwent two scan sessions per device and two repeats of each sequence per session. Repeatability and reproducibility within-subject coefficient of variation (wCV) of mean ADC were calculated for tumors and lymph nodes (patients) and parotid glands (volunteers). ADC bias, repeatability/reproducibility metrics, SNR, and geometric distortion were quantified using a phantom. RESULTS: In vivo repeatability/reproducibility wCV for parotids were 5.41%/6.72%, 3.83%/8.80%, 5.66%/10.03%, 3.44%/5.70%, 5.04%/5.66%, 4.23%/7.36% for EPI MR-linac, SPLICE, TSE, EPI MR sim, BLADE, RESOLVE. Repeatability/reproducibility wCV for EPI MR-linac, SPLICE, TSE were 9.64%/10.28%, 7.84%/8.96%, 7.60%/11.68% for tumors and 7.80%/9.95%, 7.23%/8.48%, 10.82%/10.44% for nodes. All sequences except TSE had phantom ADC biases within ±0.1x10 -3 mm 2/s for most vials (EPI MR-linac, SPLICE, and BLADE had 2, 3, and 1 vials out of 13 with larger biases, respectively). SNR of b=0 images was 87.3, 180.5, 161.3, 171.0, 171.9, 130.2 for EPI MR-linac, SPLICE, TSE, EPI MR sim, BLADE, RESOLVE. CONCLUSION: MR-linac DWI sequences demonstrated near-comparable performance to MR sim sequences and warrant further clinical validation for treatment response assessment in HNC

Assessing the Speed and Accuracy of Real-time Motion Tracking Algorithms for Abdominal Organ Motion Management in a 1.5T MR-Linac System

https://openworks.mdanderson.org/sumexp21/1166/thumbnail.jp

A look-up-table development to facilitate CT simulation of MR-Linac treatment

While current MR-Linac (MRL) treatment workflows utilize a large table overlay during CT simulation to convert indexing between the two machines, we developed a look-up-table (LUT) as an alternative approach. After populating the LUT, index conversion factors were verified at three separate table locations. The resultant root-mean-square isocenter shifts on the MRL were 0.04/0.08 cm, 0.08/0.07 cm, and 0.09/0.08 cm with/without using the table overlay during simulation in the lateral, longitudinal, and vertical directions, respectively, which is within registration tolerance. Clinical implementation of the LUT has resulted in a more efficient MRL treatment workflow while maintaining accurate patient setup

MR-Guided Adaptive Radiotherapy for OAR Sparing in Head and Neck Cancers

MR-linac devices offer the potential for advancements in radiotherapy (RT) treatment of head and neck cancer (HNC) by using daily MR imaging performed at the time and setup of treatment delivery. This article aims to present a review of current adaptive RT (ART) methods on MR-Linac devices directed towards the sparing of organs at risk (OAR) and a view of future adaptive techniques seeking to improve the therapeutic ratio. This ratio expresses the relationship between the probability of tumor control and the probability of normal tissue damage and is thus an important conceptual metric of success in the sparing of OARs. Increasing spatial conformity of dose distributions to target volume and OARs is an initial step in achieving therapeutic improvements, followed by the use of imaging and clinical biomarkers to inform the clinical decision-making process in an ART paradigm. Pre-clinical and clinical findings support the incorporation of biomarkers into ART protocols and investment into further research to explore imaging biomarkers by taking advantage of the daily MR imaging workflow. A coherent understanding of this road map for RT in HNC is critical for directing future research efforts related to sparing OARs using image-guided radiotherapy (IGRT)

MR-Guided Adaptive Radiotherapy for OAR Sparing in Head and Neck Cancers

MR-linac devices offer the potential for advancements in radiotherapy (RT) treatment of head and neck cancer (HNC) by using daily MR imaging performed at the time and setup of treatment delivery. This article aims to present a review of current adaptive RT (ART) methods on MR-Linac devices directed towards the sparing of organs at risk (OAR) and a view of future adaptive techniques seeking to improve the therapeutic ratio. This ratio expresses the relationship between the probability of tumor control and the probability of normal tissue damage and is thus an important conceptual metric of success in the sparing of OARs. Increasing spatial conformity of dose distributions to target volume and OARs is an initial step in achieving therapeutic improvements, followed by the use of imaging and clinical biomarkers to inform the clinical decision-making process in an ART paradigm. Pre-clinical and clinical findings support the incorporation of biomarkers into ART protocols and investment into further research to explore imaging biomarkers by taking advantage of the daily MR imaging workflow. A coherent understanding of this road map for RT in HNC is critical for directing future research efforts related to sparing OARs using image-guided radiotherapy (IGRT)

Assessing Therapeutic Efficacy in Real-time by Hyperpolarized Magnetic Resonance Metabolic Imaging

Precisely measuring tumor-associated alterations in metabolism clinically will enable the efficient assessment of therapeutic responses. Advances in imaging technologies can exploit the differences in cancer-associated cell metabolism as compared to normal tissue metabolism, linking changes in target metabolism to therapeutic efficacy. Metabolic imaging by Positron Emission Tomography (PET) employing 2-fluoro-deoxy-glucose ([18F]FDG) has been used as a routine diagnostic tool in the clinic. Recently developed hyperpolarized Magnetic Resonance (HP-MR), which radically increases the sensitivity of conventional MRI, has created a renewed interest in functional and metabolic imaging. The successful translation of this technique to the clinic was achieved recently with measurements of 13C-pyruvate metabolism. Here, we review the potential clinical roles for metabolic imaging with hyperpolarized MRI as applied in assessing therapeutic intervention in different cancer systems