Cluster-Based Toxicity Estimation of Osteoradionecrosis Via Unsupervised Machine Learning: Moving Beyond Single Dose-Parameter Normal Tissue Complication Probability by Using Whole Dose-Volume Histograms for Cohort Risk Stratification.

PURPOSE: Given the limitations of extant models for normal tissue complication probability estimation for osteoradionecrosis (ORN) of the mandible, the purpose of this study was to enrich statistical inference by exploiting structural properties of data and provide a clinically reliable model for ORN risk evaluation through an unsupervised-learning analysis that incorporates the whole radiation dose distribution on the mandible. METHODS AND MATERIALS: The analysis was conducted on retrospective data of 1259 patients with head and neck cancer treated at The University of Texas MD Anderson Cancer Center between 2005 and 2015. During a minimum 12-month posttherapy follow-up period, 173 patients in this cohort (13.7%) developed ORN (grades I to IV). The (structural) clusters of mandibular dose-volume histograms (DVHs) for these patients were identified using the K-means clustering method. A soft-margin support vector machine was used to determine the cluster borders and partition the dose-volume space. The risk of ORN for each dose-volume region was calculated based on incidence rates and other clinical risk factors. RESULTS: The K-means clustering method identified 6 clusters among the DVHs. Based on the first 5 clusters, the dose-volume space was partitioned by the soft-margin support vector machine into distinct regions with different risk indices. The sixth cluster entirely overlapped with the others; the region of this cluster was determined by its envelopes. For each region, the ORN incidence rate per preradiation dental extraction status (a statistically significant, nondose related risk factor for ORN) was reported as the corresponding risk index. CONCLUSIONS: This study presents an unsupervised-learning analysis of a large-scale data set to evaluate the risk of mandibular ORN among patients with head and neck cancer. The results provide a visual risk-assessment tool for ORN (based on the whole DVH and preradiation dental extraction status) as well as a range of constraints for dose optimization under different risk levels.

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.

Development and implementation of optimized endogenous contrast sequences for delineation in adaptive radiotherapy on a 1.5T MR-linear-accelerator: a prospective R-IDEAL stage 0-2a quantitative/qualitative evaluation of in vivo site-specific quality-assurance using a 3D T2 fat-suppressed platform for head and neck cancer.

Purpose: To improve segmentation accuracy in head and neck cancer (HNC) radiotherapy treatment planning for the 1.5T hybrid magnetic resonance imaging/linear accelerator (MR-Linac), three-dimensional (3D), T2-weighted, fat-suppressed magnetic resonance imaging sequences were developed and optimized. Approach: After initial testing, spectral attenuated inversion recovery (SPAIR) was chosen as the fat suppression technique. Five candidate SPAIR sequences and a nonsuppressed, T2-weighted sequence were acquired for five HNC patients using a 1.5T MR-Linac. MR physicists identified persistent artifacts in two of the SPAIR sequences, so the remaining three SPAIR sequences were further analyzed. The gross primary tumor volume, metastatic lymph nodes, parotid glands, and pterygoid muscles were delineated using five segmentors. A robust image quality analysis platform was developed to objectively score the SPAIR sequences on the basis of qualitative and quantitative metrics. Results: Sequences were analyzed for the signal-to-noise ratio and the contrast-to-noise ratio and compared with fat and muscle, conspicuity, pairwise distance metrics, and segmentor assessments. In this analysis, the nonsuppressed sequence was inferior to each of the SPAIR sequences for the primary tumor, lymph nodes, and parotid glands, but it was superior for the pterygoid muscles. The SPAIR sequence that received the highest combined score among the analysis categories was recommended to Unity MR-Linac users for HNC radiotherapy treatment planning. Conclusions: Our study led to two developments: an optimized, 3D, T2-weighted, fat-suppressed sequence that can be disseminated to Unity MR-Linac users and a robust image quality analysis pathway that can be used to objectively score SPAIR sequences and can be customized and generalized to any image quality optimization protocol. Improved segmentation accuracy with the proposed SPAIR sequence will potentially lead to improved treatment outcomes and reduced toxicity for patients by maximizing the target coverage and minimizing the radiation exposure of organs at risk.

Longitudinal diffusion and volumetric kinetics of head and neck cancer magnetic resonance on a 1.5T MR-Linear accelerator hybrid system: A prospective R-IDEAL Stage 2a imaging biomarker characterization/ pre-qualification study.

Objectives: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort. Methods: Thirty patients with pathologically confirmed HNSCC who received curative-intent RT at the University of Texas MD Anderson Cancer Center, were included in this prospective study. Baseline and weekly Magnetic resonance imaging (MRI) (weeks 1-6) were obtained, and various ADC parameters (mean, 5 th , 10 th , 20 th , 30 th , 40 th , 50 th , 60 th , 70 th , 80 th , 90 th and 95 th percentile) were extracted from the target regions of interest (ROIs). Baseline and weekly ADC parameters were correlated with response during RT, loco-regional control, and the development of recurrence using the Mann-Whitney U test. The Wilcoxon signed-rank test was used to compare the weekly ADC versus baseline values. Weekly volumetric changes (Δvolume) for each ROI were correlated with ΔADC using Spearman's Rho test. Recursive partitioning analysis (RPA) was performed to identify the optimal ΔADC threshold associated with different oncologic outcomes. Results: There was an overall significant rise in all ADC parameters during different time points of RT compared to baseline values for both gross primary disease volume (GTV-P) and gross nodal disease volumes (GTV-N). The increased ADC values for GTV-P were statistically significant only for primary tumors achieving complete remission (CR) during RT. RPA identified GTV-P ΔADC 5 th percentile >13% at the 3 rd week of RT as the most significant parameter associated with CR for primary tumor during RT (p <0.001). Baseline ADC parameters for GTV-P and GTV-N didn't significantly correlate with response to RT or other oncologic outcomes. There was a significant decrease in residual volume of both GTV-P & GTV-N throughout the course of RT. Additionally, a significant negative correlation between mean ΔADC and Δvolume for GTV-P at the 3 rd and 4 th week of RT was detected (r = -0.39, p = 0.044 & r = -0.45, p = 0.019, respectively). Conclusion: Assessment of ADC kinetics at regular intervals throughout RT seems to be correlated with RT response. Further studies with larger cohorts and multi-institutional data are needed for validation of ΔADC as a model for prediction of response to RT.

Cluster-Based Toxicity Estimation of Osteoradionecrosis via Unsupervised Machine Learning: Moving Beyond Single Dose-Parameter Normal Tissue Complication Probability by Using Whole Dose-Volume Histograms for Cohort Risk Stratification.

Purpose: Given the limitations of extant models for normal tissue complication probability estimation for osteoradionecrosis (ORN) of the mandible, the purpose of this study was to enrich statistical inference by exploiting structural properties of data and provide a clinically reliable model for ORN risk evaluation through an unsupervised-learning analysis. Materials and Methods: The analysis was conducted on retrospective data of 1,259 head and neck cancer (HNC) patients treated at the University of Texas MD Anderson Cancer Center between 2005 and 2015. The (structural) clusters of mandibular dose-volume histograms (DVHs) were identified through the K-means clustering method. A soft-margin support vector machine (SVM) was used to determine the cluster borders and partition the dose-volume space. The risk of ORN for each dose-volume region was calculated based on the clinical risk factors and incidence rates. Results: The K-means clustering method identified six clusters among the DVHs. Based on the first five clusters, the dose-volume space was partitioned almost perfectly by the soft-margin SVM into distinct regions with different risk indices. The sixth cluster overlapped the others entirely; the region of this cluster was determined by its envelops. These regions and the associated risk indices provide a range of constraints for dose optimization under different risk levels. Conclusion: This study presents an unsupervised-learning analysis of a large-scale data set to evaluate the risk of mandibular ORN among HNC patients. The results provide a visual risk-assessment tool (based on the whole DVH) and a spectrum of dose constraints for radiation planning.

Prospective validation of diffusion-weighted MRI as a biomarker of tumor response and oncologic outcomes in head and neck cancer: Results from an observational biomarker pre-qualification study.

PURPOSE: To determine DWI parameters associated with tumor response and oncologic outcomes in head and neck (HNC) patients treated with radiotherapy (RT). METHODS: HNC patients in a prospective study were included. Patients had MRIs pre-, mid-, and post-RT completion. We used T2-weighted sequences for tumor segmentation which were co-registered to respective DWIs for extraction of apparent diffusion coefficient (ADC) measurements. Treatment response was assessed at mid- and post-RT and was defined as: complete response (CR) vs. non-complete response (non-CR). The Mann-Whitney U test was used to compare ADC between CR and non-CR. Recursive partitioning analysis (RPA) was performed to identify ADC threshold associated with relapse. Cox proportional hazards models were done for clinical vs. clinical and imaging parameters and internal validation was done using bootstrapping technique. RESULTS: Eighty-one patients were included. Median follow-up was 31 months. For patients with post-RT CR, there was a significant increase in mean ADC at mid-RT compared to baseline ((1.8 ± 0.29) × 10-3 mm2/s vs. (1.37 ± 0.22) × 10-3 mm2/s, p < 0.0001), while patients with non-CR had no significant increase (p > 0.05). RPA identified GTV-P delta (Δ)ADCmean < 7% at mid-RT as the most significant parameter associated with worse LC and RFS (p = 0.01). Uni- and multi-variable analysis showed that GTV-P ΔADCmean at mid-RT ≥ 7% was significantly associated with better LC and RFS. The addition of ΔADCmean significantly improved the c-indices of LC and RFS models compared with standard clinical variables (0.85 vs. 0.77 and 0.74 vs. 0.68 for LC and RFS, respectively, p < 0.0001 for both). CONCLUSION: ΔADCmean at mid-RT is a strong predictor of oncologic outcomes in HNC. Patients with no significant increase of primary tumor ADC at mid-RT are at high risk of disease relapse.

Quality assurance assessment of intra-acquisition diffusion-weighted and T2-weighted magnetic resonance imaging registration and contour propagation for head and neck cancer radiotherapy.

BACKGROUND/PURPOSE: Adequate image registration of anatomical and functional magnetic resonance imaging (MRI) scans is necessary for MR-guided head and neck cancer (HNC) adaptive radiotherapy planning. Despite the quantitative capabilities of diffusion-weighted imaging (DWI) MRI for treatment plan adaptation, geometric distortion remains a considerable limitation. Therefore, we systematically investigated various deformable image registration (DIR) methods to co-register DWI and T2-weighted (T2W) images. MATERIALS/METHODS: We compared three commercial (ADMIRE, Velocity, Raystation) and three open-source (Elastix with default settings [Elastix Default], Elastix with parameter set 23 [Elastix 23], Demons) post-acquisition DIR methods applied to T2W and DWI MRI images acquired during the same imaging session in twenty immobilized HNC patients. In addition, we used the non-registered images (None) as a control comparator. Ground-truth segmentations of radiotherapy structures (tumour and organs at risk) were generated by a physician expert on both image sequences. For each registration approach, structures were propagated from T2W to DWI images. These propagated structures were then compared with ground-truth DWI structures using the Dice similarity coefficient and mean surface distance. RESULTS: 19 left submandibular glands, 18 right submandibular glands, 20 left parotid glands, 20 right parotid glands, 20 spinal cords, and 12 tumours were delineated. Most DIR methods took <30 s to execute per case, with the exception of Elastix 23 which took ∼458 s to execute per case. ADMIRE and Elastix 23 demonstrated improved performance over None for all metrics and structures (Bonferroni-corrected p < 0.05), while the other methods did not. Moreover, ADMIRE and Elastix 23 significantly improved performance in individual and pooled analysis compared to all other methods. CONCLUSIONS: The ADMIRE DIR method offers improved geometric performance with reasonable execution time so should be favoured for registering T2W and DWI images acquired during the same scan session in HNC patients. These results are important to ensure the appropriate selection of registration strategies for MR-guided radiotherapy.

Deep-learning-based generation of synthetic 6-minute MRI from 2-minute MRI for use in head and neck cancer radiotherapy.

Background: Quick magnetic resonance imaging (MRI) scans with low contrast-to-noise ratio are typically acquired for daily MRI-guided radiotherapy setup. However, for patients with head and neck (HN) cancer, these images are often insufficient for discriminating target volumes and organs at risk (OARs). In this study, we investigated a deep learning (DL) approach to generate high-quality synthetic images from low-quality images. Methods: We used 108 unique HN image sets of paired 2-minute T2-weighted scans (2mMRI) and 6-minute T2-weighted scans (6mMRI). 90 image sets (~20,000 slices) were used to train a 2-dimensional generative adversarial DL model that utilized 2mMRI as input and 6mMRI as output. Eighteen image sets were used to test model performance. Similarity metrics, including the mean squared error (MSE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR) were calculated between normalized synthetic 6mMRI and ground-truth 6mMRI for all test cases. In addition, a previously trained OAR DL auto-segmentation model was used to segment the right parotid gland, left parotid gland, and mandible on all test case images. Dice similarity coefficients (DSC) were calculated between 2mMRI and either ground-truth 6mMRI or synthetic 6mMRI for each OAR; two one-sided t-tests were applied between the ground-truth and synthetic 6mMRI to determine equivalence. Finally, a visual Turing test using paired ground-truth and synthetic 6mMRI was performed using three clinician observers; the percentage of images that were correctly identified was compared to random chance using proportion equivalence tests. Results: The median similarity metrics across the whole images were 0.19, 0.93, and 33.14 for MSE, SSIM, and PSNR, respectively. The median of DSCs comparing ground-truth vs. synthetic 6mMRI auto-segmented OARs were 0.86 vs. 0.85, 0.84 vs. 0.84, and 0.82 vs. 0.85 for the right parotid gland, left parotid gland, and mandible, respectively (equivalence p<0.05 for all OARs). The percent of images correctly identified was equivalent to chance (p<0.05 for all observers). Conclusions: Using 2mMRI inputs, we demonstrate that DL-generated synthetic 6mMRI outputs have high similarity to ground-truth 6mMRI, but further improvements can be made. Our study facilitates the clinical incorporation of synthetic MRI in MRI-guided radiotherapy.

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).

Metabolic Imaging Using Hyperpolarization for Assessment of Premalignancy.

There is an unmet need for noninvasive surrogate markers that can help identify premalignant lesions across different tumor types. Here we describe the methodology and technical details of protocols employed for in vivo 13C pyruvate metabolic imaging experiments. The goal of the method described is to identify and understand metabolic changes, to enable detection of pancreatic premalignant lesions, as a proof of concept of the high sensitivity of this imaging modality.

Measuring the Metabolic Evolution of Glioblastoma throughout Tumor Development, Regression, and Recurrence with Hyperpolarized Magnetic Resonance.

Rapid diagnosis and therapeutic monitoring of aggressive diseases such as glioblastoma can improve patient survival by providing physicians the time to optimally deliver treatment. This research tested whether metabolic imaging with hyperpolarized MRI could detect changes in tumor progression faster than conventional anatomic MRI in patient-derived glioblastoma murine models. To capture the dynamic nature of cancer metabolism, hyperpolarized MRI, NMR spectroscopy, and immunohistochemistry were performed at several time-points during tumor development, regression, and recurrence. Hyperpolarized MRI detected significant changes of metabolism throughout tumor progression whereas conventional MRI was less sensitive. This was accompanied by aberrations in amino acid and phospholipid lipid metabolism and MCT1 expression. Hyperpolarized MRI can help address clinical challenges such as identifying malignant disease prior to aggressive growth, differentiating pseudoprogression from true progression, and predicting relapse. The individual evolution of these metabolic assays as well as their correlations with one another provides context for further academic research.

Advances in Imaging for HPV-Related Oropharyngeal Cancer: Applications to Radiation Oncology.

While there has been an overall decline of tobacco and alcohol-related head and neck cancer in recent decades, there has been an increased incidence of HPV-associated oropharyngeal cancer (OPC). Recent research studies and clinical trials have revealed that the cancer biology and clinical progression of HPV-positive OPC is unique relative to its HPV-negative counterparts. HPV-positive OPC is associated with higher rates of disease control following definitive treatment when compared to HPV-negative OPC. Thus, these conditions should be considered unique diseases with regards to treatment strategies and survival. In order to sufficiently characterize HPV-positive OPC and guide treatment strategies, there has been a considerable effort to diagnose, prognose, and track the treatment response of HPV-associated OPC through advanced imaging research. Furthermore, HPV-positive OPC patients are prime candidates for radiation de-escalation protocols, which will ideally reduce toxicities associated with radiation therapy and has prompted additional imaging research to detect radiation-induced changes in organs at risk. This manuscript reviews the various imaging modalities and current strategies for tackling these challenges as well as provides commentary on the potential successes and suggested improvements for the optimal treatment of these tumors.

Combining Hyperpolarized Real-Time Metabolic Imaging and NMR Spectroscopy To Identify Metabolic Biomarkers in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that progresses without any symptom, and oftentimes, it is detected at an advanced stage. The lack of prior symptoms and effective treatments have created a knowledge gap in the management of this lethal disease. This issue can be addressed by developing novel noninvasive imaging-based biomarkers in PDAC. We explored in vivo hyperpolarized (HP) 13C MRS of pyruvate to lactate conversion and ex vivo 1H NMR spectroscopy in a panel of well-annotated patient-derived PDAC xenograft (PDXs) model and investigated the correlation between aberrant glycolytic metabolism and aggressiveness of the tumor. Real-time metabolic imaging data demonstrate the immediate intracellular conversion of HP 13C pyruvate to lactate after intravenous injection interrogating upregulated lactate dehydrogenase (LDH) activity in aggressive PDXs. Total ex vivo lactate measurement by 1H NMR spectroscopy showed a direct correlation with in vivo dynamic pyruvate-to-lactate conversion and demonstrated the potential of dynamic metabolic flux as a biomarker of total lactate concentration and aggressiveness of the tumor. Furthermore, the metabolite concentrations were very distinct among all four tumor types analyzed in this study. Overexpression of LDH-A and hypoxia-inducible factor (HIF-1α) plays a significant role in the conversion kinetics of HP pyruvate-to-lactate in tumors. Collectively, these data identified aberrant metabolic characteristics of pancreatic cancer PDXs and could potentially delineate metabolic targets for therapeutic intervention. Metabolic imaging with HP pyruvate and NMR metabolomics may enable identification and classification of aggressive subtypes of patient-derived xenografts. Translation of this real-time metabolic technique to the clinic may have the potential to improve the management of patients at high risk of developing pancreatic diseases.

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.

Education-dependent activation of glycolysis promotes the cytolytic potency of licensed human natural killer cells.

BACKGROUND: The mechanism by which natural killer (NK) cell education results in licensed NK cells with heightened effector function against missing self-targets is not known. OBJECTIVE: We sought to identify potential mechanisms of enhanced function in licensed human NK cells. METHODS: We used expanded human NK cells from killer immunoglobulin-like receptor (KIR)/HLA-genotyped donors sorted for single-KIR+ cells to generate pure populations of licensed and unlicensed NK cells. We performed proteomic and gene expression analysis of these cells before and after receptor cross-linking and performed functional and metabolic analysis before and after interference with selected metabolic pathways. We verified key findings using freshly isolated and sorted NK cells from peripheral blood. RESULTS: We confirmed that licensed human NK cells are greater in number in peripheral blood and proliferate more in vitro than unlicensed NK cells. Using high-throughput protein analysis, we found that unstimulated licensed NK cells have increased expression of the glycolytic enzyme pyruvate kinase muscle isozyme M2 and after KIR cross-linking have increased phosphorylation of the metabolic modulators p38-α and 5' adenosine monophosphate-activated protein kinase α. After cytokine expansion and activation, unlicensed NK cells depended solely on mitochondrial respiration for cytolytic function, whereas licensed NK cells demonstrated metabolic reprogramming toward glycolysis and mitochondrial-dependent glutaminolysis, leading to accumulation of glycolytic metabolites and depletion of glutamate. As such, blocking both glycolysis and mitochondrial-dependent respiration was required to suppress the cytotoxicity of licensed NK cells. CONCLUSIONS: Collectively, our data support an arming model of education in which enhanced glycolysis in licensed NK cells supports proliferative and cytotoxic capacity.

Prostate Cancer Energetics and Biosynthesis.

Cancers must alter their metabolism to satisfy the increased demand for energy and to produce building blocks that are required to create a rapidly growing tumor. Further, for cancer cells to thrive, they must also adapt to an often changing tumor microenvironment, which can present new metabolic challenges (ex. hypoxia) that are unfavorable for most other cells. As such, altered metabolism is now considered an emerging hallmark of cancer. Like many other malignancies, the metabolism of prostate cancer is considerably different compared to matched benign tissue. However, prostate cancers exhibit distinct metabolic characteristics that set them apart from many other tumor types. In this chapter, we will describe the known alterations in prostate cancer metabolism that occur during initial tumorigenesis and throughout disease progression. In addition, we will highlight upstream regulators that control these metabolic changes. Finally, we will discuss how this new knowledge is being leveraged to improve patient care through the development of novel biomarkers and metabolically targeted therapies.

Interrogating IDH Mutation in Brain Tumor: Magnetic Resonance and Hyperpolarization.

Magnetic resonance spectroscopy (MRS) offers the possibility to noninvasively quantify 2HG concentration in the brain in the clinic, thereby serving as a valuable tool for patient-stratification as well as targeted treatment monitoring. Recently, hyperpolarized magnetic resonance techniques have opened up new opportunities for metabolic imaging not possible with conventional MRS in the brain. With over 10,000-fold increase in signal-to-noise ratio (SNR), dynamic metabolic processes can be interrogated in vivo with very high specificity by hyperpolarized MRI. In the following article, we will review relevant clinical studies and practical considerations of MRS and hyperpolarized MRS, as well as discuss some promising preclinical hyperpolarization studies to interrogate real-time metabolism in IDH mutations in vivo.

Interrogating Metabolism in Brain Cancer.

This article reviews existing and emerging techniques of interrogating metabolism in brain cancer from well-established proton magnetic resonance spectroscopy to the promising hyperpolarized metabolic imaging and chemical exchange saturation transfer and emerging techniques of imaging inflammation. Some of these techniques are at an early stage of development and clinical trials are in progress in patients to establish the clinical efficacy. It is likely that in vivo metabolomics and metabolic imaging is the next frontier in brain cancer diagnosis and assessing therapeutic efficacy; with the combined knowledge of genomics and proteomics a complete understanding of tumorigenesis in brain might be achieved.