Quantification of perineural satellitosis in pretreatment glioblastoma with structural MRI and a diffusion tensor imaging template.

Background: Survival outcomes for glioblastoma (GBM) patients remain unfavorable, and tumor recurrence is often observed. Understanding the radiological growth patterns of GBM could aid in improving outcomes. This study aimed to examine the relationship between contrast-enhancing tumor growth direction and white matter, using an image registration and deformation strategy. Methods: In GBM patients 2 pretreatment scans (diagnostic and neuronavigation) were gathered retrospectively, and coregistered to a template and diffusion tensor imaging (DTI) atlas. The GBM lesions were segmented and coregistered to the same space. Growth vectors were derived and divided into vector populations parallel (Φ = 0-20°) and perpendicular (Φ = 70-90°) to white matter. To test for statistical significance between parallel and perpendicular groups, a paired samples Student's t-test was performed. O6-methylguanine-DNA methyltransferase (MGMT) methylation status and its correlation to growth rate were also tested using a one-way ANOVA test. Results: For 78 GBM patients (mean age 61 years ±â€…13 SD, 32 men), the included GBM lesions showed a predominant preference for perineural satellitosis (P < .001), with a mean percentile growth of 30.8% (95% CI: 29.6-32.0%) parallel (0°â€…< |Φ| < 20°) to white matter. Perpendicular tumor growth with respect to white matter microstructure (70°â€…< |Φ| < 90°) showed to be 22.7% (95% CI: 21.3-24.1%) of total tumor growth direction. Conclusions: The presented strategy showed that tumor growth direction in pretreatment GBM patients correlated with white matter architecture. Future studies with patient-specific DTI data are required to verify the accuracy of this method prospectively to identify its usefulness as a clinical metric in pre and posttreatment settings.

In Vivo Magnetic Resonance Spectroscopy Methods for Investigating Cardiac Metabolism.

Magnetic resonance spectroscopy (MRS) is a non-invasive and non-ionizing technique, enabling in vivo investigation of cardiac metabolism in normal and diseased hearts. In vivo measurement tools are critical for studying mechanisms that regulate cardiac energy metabolism in disease developments and to assist in early response assessments to novel therapies. For cardiac MRS, proton (1H), phosphorus (31P), and hyperpolarized 13-carbon (13C) provide valuable metabolic information for diagnosis and treatment assessment purposes. Currently, low sensitivity and some technical limitations limit the utility of MRS. An essential step in translating MRS for clinical use involves further technological improvements, particularly in coil design, improving the signal-to-noise ratios, field homogeneity, and optimizing radiofrequency sequences. This review addresses the recent advances in metabolic imaging by MRS from primarily the literature published since 2015.

Diffusion tension imaging is a good tool for assessing patients with dementia and behavioral problems and discriminating them from other dementia patients.

BACKGROUND: Dementia is one of the leading public health concerns as the world's population ages. Although Alzheimer's disease (AD) is the most common dementia diagnosis among older patients, some patients have additional behavioral symptoms. It is therefore important to provide an exact diagnosis, both to provide the best possible treatment for patients and to facilitate better understanding. PURPOSE: To investigate whether magnetic resonance imaging (MRI) with fractional anisotropy (FA) can accurately find patients with behavioral symptoms within a group of AD patients. MATERIAL AND METHODS: Forty-five patients from the geriatric outpatient clinic were recruited consecutively to form a group of patients with AD and behavioral symptoms (AD + BS) and a control group of 50 patients with established AD. All patients had a full assessment for dementia to establish the diagnosis according to ICD-10. MRI included 3D anatomical recordings for morphometric measurements, DTI for fiber tracking, and quantitative assessment of regional white matter integrity. The DTI analyses included computing of the diffusion tensor and its derived FA index. RESULTS: We found a significant difference in FA values between the patient groups' frontal lobes. The FA was greater in the study group in both left (0.39 vs 0.09, p < 0.05) and right (0.40 vs 0.16, p < 0.05) frontal lobes. CONCLUSION: MRI with FA will find damage in frontal tracts and may be used as a diagnostic tool and be considered a robust tool for the recognizing different types of dementia in the future.

Explainable Artificial Intelligence for Human-Machine Interaction in Brain Tumor Localization.

Primary malignancies in adult brains are globally fatal. Computer vision, especially recent developments in artificial intelligence (AI), have created opportunities to automatically characterize and diagnose tumor lesions in the brain. AI approaches have provided scores of unprecedented accuracy in different image analysis tasks, including differentiating tumor-containing brains from healthy brains. AI models, however, perform as a black box, concealing the rational interpretations that are an essential step towards translating AI imaging tools into clinical routine. An explainable AI approach aims to visualize the high-level features of trained models or integrate into the training process. This study aims to evaluate the performance of selected deep-learning algorithms on localizing tumor lesions and distinguishing the lesion from healthy regions in magnetic resonance imaging contrasts. Despite a significant correlation between classification and lesion localization accuracy (R = 0.46, p = 0.005), the known AI algorithms, examined in this study, classify some tumor brains based on other non-relevant features. The results suggest that explainable AI approaches can develop an intuition for model interpretability and may play an important role in the performance evaluation of deep learning models. Developing explainable AI approaches will be an essential tool to improve human-machine interactions and assist in the selection of optimal training methods.

Whole-Slab 3D MR Spectroscopic Imaging of the Human Brain With Spiral-Out-In Sampling at 7T.

BACKGROUND: Metabolic imaging using proton magnetic resonance spectroscopic imaging (MRSI) has increased the sensitivity and spectral resolution at field strengths of ≥7T. Compared to the conventional Cartesian-based spectroscopic imaging, spiral trajectories enable faster data collection, promising the clinical translation of whole-brain MRSI. Technical considerations at 7T, however, lead to a suboptimal sampling efficiency for the spiral-out (SO) acquisitions, as a significant portion of the trajectory consists of rewinders. PURPOSE: To develop and implement a spiral-out-in (SOI) trajectory for sampling of whole-brain MRSI at 7T. We hypothesized that SOI will improve the signal-to-noise ratio (SNR) of metabolite maps due to a more efficient acquisition. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: Five healthy volunteers (28-38 years, three females) and a phantom. FIELD STRENGTH/SEQUENCE: Navigated adiabatic spin-echo spiral 3D MRSI at 7T. ASSESSMENT: A 3D stack of SOI trajectories was incorporated into an adiabatic spin-echo MRSI sequence with real-time motion and shim correction. Metabolite spectral fitting, SNR, and Cramér-Rao lower bound (CRLB) were obtained. We compared the signal intensity and CRLB of three metabolites of tNAA, tCr, and tCho. Peak SNR (PSNR), structure similarity index (SSIM), and signal-to-artifact ratio were evaluated on water maps. STATISTICAL TESTS: The nonparametric Mann-Whitney U-test was used for statistical testing. RESULTS: Compared to SO, the SOI trajectory: 1) increased the k-space sampling efficiency by 23%; 2) is less demanding for the gradient hardware, requiring 36% lower Gmax and 26% lower Smax ; 3) increased PSNR of water maps by 4.94 dB (P = 0.0006); 4) resulted in a 29% higher SNR (P = 0.003) and lower CRLB by 26-35% (P = 0.02, tNAA), 35-55% (P = 0.03, tCr), and 22-23% (P = 0.04, tCho), which increased the number of well-fitted voxels (eg, for tCr by 11%, P = 0.03). SOI did not significantly change the signal-to-artifact ratio and SSIM (P = 0.65) compared to SO. DATA CONCLUSION: SOI provided more efficient MRSI at 7T compared to SO, which improved the data quality and metabolite quantification. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

An integrated RF-receive/B0-shim array coil boosts performance of whole-brain MR spectroscopic imaging at 7 T.

Metabolic imaging of the human brain by in-vivo magnetic resonance spectroscopic imaging (MRSI) can non-invasively probe neurochemistry in healthy and disease conditions. MRSI at ultra-high field (≥ 7 T) provides increased sensitivity for fast high-resolution metabolic imaging, but comes with technical challenges due to non-uniform B0 field. Here, we show that an integrated RF-receive/B0-shim (AC/DC) array coil can be used to mitigate 7 T B0 inhomogeneity, which improves spectral quality and metabolite quantification over a whole-brain slab. Our results from simulations, phantoms, healthy and brain tumor human subjects indicate improvements of global B0 homogeneity by 55%, narrower spectral linewidth by 29%, higher signal-to-noise ratio by 31%, more precise metabolite quantification by 22%, and an increase by 21% of the brain volume that can be reliably analyzed. AC/DC shimming provide the highest correlation (R2 = 0.98, P = 0.001) with ground-truth values for metabolite concentration. Clinical translation of AC/DC and MRSI is demonstrated in a patient with mutant-IDH1 glioma where it enables imaging of D-2-hydroxyglutarate oncometabolite with a 2.8-fold increase in contrast-to-noise ratio at higher resolution and more brain coverage compared to previous 7 T studies. Hence, AC/DC technology may help ultra-high field MRSI become more feasible to take advantage of higher signal/contrast-to-noise in clinical applications.

A Review of Different Aspects of Applying Asphalt and Bituminous Mixes under a Railway Track.

Asphalt is a common material that is used extensively for roadways. Furthermore, bituminous mixes have been used in railways, both as asphalt and as mortar. Different agencies and research institutes have investigated and suggested various applications. These studies indicate the benefits of bituminous material under railways, such as improving a substructure's stiffness and bearing capacity; enhancing its dynamic characteristics and response, especially under high-speed train loads; waterproofing the subgrade; protecting the top layers against fine contamination. These potential applications can improve the overall track structure performance and lead to minimizing settlement under heavy loads. They can also guarantee an appropriate response under high-speed loads, especially in comparison to a rigid slab track. This review paper documents the literature related to the utilization of asphalt and bituminous mixes in railway tracks. This paper presents a critical review of the research in the application of asphalt and bituminous mixes in railway tracks. Additionally, this paper reviews the design and construction recommendations and procedures for asphalt and bituminous mixes in railway tracks as practiced in different countries. This paper also provides case studies of projects where asphalt and bituminous mixes have been utilized in railway tracks. It is anticipated that this review paper will facilitate (1) the exchange of ideas and innovations in the area of the design and construction of railway tracks and (2) the development of unified standards for the design and construction of railway tracks with asphalt and bituminous mixtures.

Effect of exercise training on cardiac metabolism in rats with heart failure.

Objectives. Heart failure (HF) impairs resting myocardial energetics, myocardial mitochondrial performance, and maximal oxygen uptake (VO2max). Exercise training is included in most rehabilitation programs and benefits HF patients. However, the effect of exercise intensity on cardiac mitochondrial respiration and concentrations of the key bioenergetic metabolites phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi) is unclear. This study aimed to investigate the effects of exercise training at different intensities in rats with HF. Methods. Rats underwent myocardial infarction or sham operations and were divided into three subgroups: sedentary, moderate intensity, or high intensity. The impact of HF and 6 weeks of exercise training on energy metabolism was evaluated by 31P magnetic resonance spectroscopy and mitochondrial respirometry. The concentrations of PCr, ATP, and Pi were quantified by magnetic resonance spectroscopy. VO2max was measured by treadmill respirometry. Results. Exercise training increased VO2max in sham and HF. PCr/ATP ratio was reduced in HF (p < .01) and remained unchanged by exercise training. PCr concentration was significantly lower in HF compared to sham (p < .01). Moderate and high-intensity exercise training increased ATP in HF and sham. HF impaired complex I (CI) and complex II (p = .034) respiration. High-intensity exercise training recovered CI respiration in HF rats compared to HF sedentary (p = .014). Conclusions. Exercise training improved cardiac performance, as indicated by increased VO2max and higher exercise capacity, without changing the myocardial PCr/ATP ratio. These observations suggest that the PCr/ATP biomarker is not suited to evaluate the beneficial effects of exercise training in the heart. The exact mechanisms require further investigations, as exercise training did increase ATP levels and CI respiration.

The Effect of Exercise Training on Myocardial and Skeletal Muscle Metabolism by MR Spectroscopy in Rats with Heart Failure.

The metabolism and performance of myocardial and skeletal muscle are impaired in heart failure (HF) patients. Exercise training improves the performance and benefits the quality of life in HF patients. The purpose of the present study was to determine the metabolic profiles in myocardial and skeletal muscle in HF and exercise training using MRS, and thus to identify targets for clinical MRS in vivo. After surgically establishing HF in rats, we randomized the rats to exercise training programs of different intensities. After the final training session, rats were sacrificed and tissues from the myocardial and skeletal muscle were extracted. Magnetic resonance spectra were acquired from these extracts, and principal component and metabolic enrichment analysis were used to assess the differences in metabolic profiles. The results indicated that HF affected myocardial metabolism by changing multiple metabolites, whereas it had a limited effect on skeletal muscle metabolism. Moreover, exercise training mainly altered the metabolite distribution in skeletal muscle, indicating regulation of metabolic pathways of taurine and hypotaurine metabolism and carnitine synthesis.

Simultaneous 18F-fluciclovine Positron Emission Tomography and Magnetic Resonance Spectroscopic Imaging of Prostate Cancer.

Purpose: To investigate the associations of metabolite levels derived from magnetic resonance spectroscopic imaging (MRSI) and 18F-fluciclovine positron emission tomography (PET) with prostate tissue characteristics. Methods: In a cohort of 19 high-risk prostate cancer patients that underwent simultaneous PET/MRI, we evaluated the diagnostic performance of MRSI and PET for discrimination of aggressive cancer lesions from healthy tissue and benign lesions. Data analysis comprised calculations of correlations of mean standardized uptake values (SUVmean), maximum SUV (SUVmax), and the MRSI-derived ratio of (total choline + spermine + creatine) to citrate (CSC/C). Whole-mount histopathology was used as gold standard. Results: The results showed a moderate significant correlation between both SUVmean and SUVmax with CSC/C ratio. Conclusions: We demonstrated that the simultaneous acquisition of 18F-fluciclovine PET and MRSI with an integrated PET/MRI system is feasible and a combination of these imaging modalities has potential to improve the diagnostic sensitivity and specificity of prostate cancer lesions.

Skeletal muscle metabolism in rats with low and high intrinsic aerobic capacity: Effect of aging and exercise training.

PURPOSE: Exercise training increases aerobic capacity and is beneficial for health, whereas low aerobic exercise capacity is a strong independent predictor of cardiovascular disease and premature death. The purpose of the present study was to determine the metabolic profiles in a rat model of inborn low versus high capacity runners (LCR/HCR) and to determine the effect of inborn aerobic capacity, aging, and exercise training on skeletal muscle metabolic profile. METHODS: LCR/HCR rats were randomized to high intensity low volume interval treadmill training twice a week or sedentary control for 3 or 11 months before they were sacrificed, at 9 and 18 months of age, respectively. Magnetic resonance spectra were acquired from soleus muscle extracts, and partial least square discriminative analysis was used to determine the differences in metabolic profile. RESULTS: Sedentary HCR rats had 54% and 30% higher VO2max compared to sedentary LCR rats at 9 months and 18 months, respectively. In HCR, exercise increased running speed significantly, and VO2max was higher at age of 9 months, compared to sedentary counterparts. In LCR, changes were small and did not reach the level of significance. The metabolic profile was significantly different in the LCR sedentary group compared to the HCR sedentary group at the age of 9 and 18 months, with higher glutamine and glutamate levels (9 months) and lower lactate level (18 months) in HCR. Irrespective of fitness level, aging was associated with increased soleus muscle concentrations of glycerophosphocholine and glucose. Interval training did not influence metabolic profiles in LCR or HCR rats at any age. CONCLUSION: Differences in inborn aerobic capacity gave the most marked contrasts in metabolic profile, there were also some changes with ageing. Low volume high intensity interval training twice a week had no detectable effect on metabolic profile.

The Direction of Tumour Growth in Glioblastoma Patients.

Generating MR-derived growth pattern models for glioblastoma multiforme (GBM) has been an attractive approach in neuro-oncology, suggesting a distinct pattern of lesion spread with a tendency in growing along the white matter (WM) fibre direction for the invasive component. However, the direction of growth is not much studied in vivo. In this study, we sought to study the dominant directions of tumour expansion/shrinkage pre-treatment. We examined fifty-six GBMs at two time-points: at radiological diagnosis and as part of the pre-operative planning, both with contrast-enhanced T1-weighted MRIs. The tumour volumes were semi-automatically segmented. A non-linear registration resulting in a deformation field characterizing the changes between the two time points was used together with the segmented tumours to determine the dominant directions of tumour change. To compute the degree of alignment between tumour growth vectors and WM fibres, an angle map was calculated. Our results demonstrate that tumours tend to grow predominantly along the WM, as evidenced by the dominant vector population with the maximum alignments. Our findings represent a step forward in investigating the hypothesis that tumour cells tend to migrate preferentially along the WM.

In vivo MR spectroscopy predicts high tumor grade in endometrial cancer.

Background In vivo magnetic resonance spectroscopy (MRS) enables non-invasive measurements of tumor metabolites. Choline-containing metabolites play a key role in tumor metabolism. Purpose To explore whether preoperative MRS-derived tumor choline levels are associated with clinical and histological features in endometrial carcinomas. Material and Methods Preoperative pelvic magnetic resonance imaging (MRI) (1.5T), including structural and diffusion-weighted imaging and localized multivoxel proton MR (1H-MR) spectroscopy, was performed in 77 prospectively included patients with histologically confirmed endometrial carcinomas. Relative levels of total choline-containing metabolites (tCho) in tumor and myometrium were measured using the ratios: tCho/Creatine; tCho/Water; and tCho/Noise. MRS parameters were analyzed in relation to histological subtype and grade, surgicopathological staging parameters, MRI-measured tumor volume, and tumor apparent diffusion coefficient (ADC) value and clinical outcome. Results Tumor tissue had significantly higher ratios for tCho/Creatine, tCho/Water, and tCho/Noise than normal myometrial tissue ( P < 0.001 for all). High tumor tCho/Water ratio was significantly associated with high tumor grade in endometrioid tumors ( P = 0.02). Tumor tCho/Creatine ratio was positively correlated to MRI-measured tumor volume (rs = 0.25; P = 0.03). Conclusion High choline levels in tumor are associated with high-risk features. In vivo MRS may potentially aid in the preoperative risk stratification in endometrial cancer.

Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival.

Precise assessment of treatment response in glioblastoma during combined anti-angiogenic and chemoradiation remains a challenge. In particular, early detection of treatment response by standard anatomical imaging is confounded by pseudo-response or pseudo-progression. Metabolic changes may be more specific for tumor physiology and less confounded by changes in blood-brain barrier permeability. We hypothesize that metabolic changes probed by magnetic resonance spectroscopic imaging can stratify patient response early during combination therapy. We performed a prospective longitudinal imaging study in newly diagnosed glioblastoma patients enrolled in a phase II clinical trial of the pan-vascular endothelial growth factor receptor inhibitor cediranib in combination with standard fractionated radiation and temozolomide (chemoradiation). Forty patients were imaged weekly during therapy with an imaging protocol that included magnetic resonance spectroscopic imaging, perfusion magnetic resonance imaging, and anatomical magnetic resonance imaging. Data were analyzed using receiver operator characteristics, Cox proportional hazards model, and Kaplan-Meier survival plots. We observed that the ratio of total choline to healthy creatine after 1 month of treatment was significantly associated with overall survival, and provided as single parameter: (1) the largest area under curve (0.859) in receiver operator characteristics, (2) the highest hazard ratio (HR = 85.85, P = 0.006) in Cox proportional hazards model, (3) the largest separation (P = 0.004) in Kaplan-Meier survival plots. An inverse correlation was observed between total choline/healthy creatine and cerebral blood flow, but no significant relation to tumor volumetrics was identified. Our results suggest that in vivo metabolic biomarkers obtained by magnetic resonance spectroscopic imaging may be an early indicator of response to anti-angiogenic therapy combined with standard chemoradiation in newly diagnosed glioblastoma.

Multimodal 18F-Fluciclovine PET/MRI and Ultrasound-Guided Neurosurgery of an Anaplastic Oligodendroglioma.

BACKGROUND: Structural magnetic resonance imaging (MRI) and histopathologic tissue sampling are routinely performed as part of the diagnostic workup for patients with glioma. Because of the heterogeneous nature of gliomas, there is a risk of undergrading caused by histopathologic sampling errors. MRI has limitations in identifying tumor grade and type, detecting diffuse invasive growth, and separating recurrences from treatment induced changes. Positron emission tomography (PET) can provide quantitative information of cellular activity and metabolism, and may therefore complement MRI. In this report, we present the first patient with brain glioma examined with simultaneous PET/MRI using the amino acid tracer 18F-fluciclovine (18F-FACBC) for intraoperative image-guided surgery. CASE DESCRIPTION: A previously healthy 60-year old woman was admitted to the emergency care with speech difficulties and a mild left-sided hemiparesis. MRI revealed a tumor that was suggestive of glioma. Before surgery, the patient underwent a simultaneous PET/MRI examination. Fused PET/MRI, T1, FLAIR, and intraoperative three-dimensional ultrasound images were used to guide histopathologic tissue sampling and surgical resection. Navigated, image-guided histopathologic samples were compared with PET/MRI image data to assess the additional value of the PET acquisition. Histopathologic analysis showed anaplastic oligodendroglioma in the most malignant parts of the tumor, while several regions were World Health Organization (WHO) grade II. CONCLUSIONS: 18F-Fluciclovine uptake was found in parts of the tumor where regional WHO grade, cell proliferation, and cell densities were highest. This finding suggests that PET/MRI with this tracer could be used to improve accuracy in histopathologic tissue sampling and grading, and possibly for guiding treatments targeting the most malignant part of extensive and eloquent gliomas.

Three-dimensional MR spectroscopic imaging using adiabatic spin echo and hypergeometric dual-band suppression for metabolic mapping over the entire brain.

PURPOSE: Large lipid and water signals in MR spectroscopic imaging (MRSI) complicate brain metabolite quantification. In this study, we combined adiabatic hypergeometric dual-band (HGDB) lipid and water suppression with gradient offset independent adiabatic (GOIA) spin echo to improve three-dimensional (3D) MRSI of the entire brain. METHODS: 3D MRSI was acquired at 3T with a 32-channel coil. HGDB pulses were used before excitation and during echo time. A brain slab was selected with GOIA-W(16,4) pulses, weighted phase encoded stack of spirals, and real-time motion/shim correction. HGDB alone or in combination with OVS and MEGA (MEscher-GArwood) was compared with OVS only and no suppression. RESULTS: The combined HGDB pulses suppressed lipids to 2%-3% of their full unsuppressed signal. The HGDB lipid suppression was on average 5 times better than OVS suppression. HGDB+MEGA provided 30% more suppression compared with a previously described HGDB+OVS scheme. The number of voxels with good metabolic fits was significantly larger in the HGDB data (91%-94%) compared with the OVS data (59%-80%). CONCLUSION: HGDB pulses provided efficient lipid and water suppression for full brain 3D MRSI. The HGDB suppression is superior to traditional OVS, and it can be combined with adiabatic spin echo to provide a sequence that is robust to B1 inhomogeneity. Magn Reson Med 77:490-497, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

1D-spectral editing and 2D multispectral in vivo1H-MRS and 1H-MRSI - Methods and applications.

This article reviews the methodological aspects of detecting low-abundant J-coupled metabolites via 1D spectral editing techniques and 2D nuclear magnetic resonance (NMR) methods applied in vivo, in humans, with a focus on the brain. A brief explanation of the basics of J-evolution will be followed by an introduction to 1D spectral editing techniques (e.g., J-difference editing, multiple quantum coherence filtering) and 2D-NMR methods (e.g., correlation spectroscopy, J-resolved spectroscopy). Established and recently developed methods will be discussed and the most commonly edited J-coupled metabolites (e.g., neurotransmitters, antioxidants, onco-markers, and markers for metabolic processes) will be briefly summarized along with their most important applications in neuroscience and clinical diagnosis.

In vivo ³¹P magnetic resonance spectroscopic imaging (MRSI) for metabolic profiling of human breast cancer xenografts.

PURPOSE: To study cancer associated with abnormal metabolism of phospholipids, of which several have been proposed as biomarkers for malignancy or to monitor response to anticancer therapy. We explored 3D (31) P magnetic resonance spectroscopic imaging (MRSI) at high magnetic field for in vivo assessment of individual phospholipids in two patient-derived breast cancer xenografts representing good and poor prognosis (luminal- and basal-like tumors). MATERIALS AND METHODS: Metabolic profiles from luminal-like and basal-like xenograft tumors were obtained in vivo using 3D (31) P MRSI at 11.7T and from tissue extracts in vitro at 14.1T. Gene expression analysis was performed in order to support metabolic differences between the two xenografts. RESULTS: In vivo (31) P MR spectra were obtained in which the prominent resonances from phospholipid metabolites were detected at a high signal-to-noise ratio (SNR >7.5). Metabolic profiles obtained in vivo were in agreement with those obtained in vitro and could be used to discriminate between the two xenograft models, based on the levels of phosphocholine, phosphoethanolamine, glycerophosphocholine, and glycerophosphoethanolamine. The differences in phospholipid metabolite concentration could partly be explained by gene expression profiles. CONCLUSION: Noninvasive metabolic profiling by 3D (31) P MRSI can discriminate between subtypes of breast cancer based on different concentrations of choline- and ethanolamine-containing phospholipids.

IDH1 R132H mutation generates a distinct phospholipid metabolite profile in glioma.

Many patients with glioma harbor specific mutations in the isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. Because IDH1 also regulates several pathways leading to lipid synthesis, we hypothesized that IDH1-mutant tumors have an altered phospholipid metabolite profile that would impinge on tumor pathobiology. To investigate this hypothesis, we performed (31)P-MRS imaging in mouse xenograft models of four human gliomas, one of which harbored the IDH1-R132H mutation. (31)P-MR spectra from the IDH1-mutant tumor displayed a pattern distinct from that of the three IDH1 wild-type tumors, characterized by decreased levels of phosphoethanolamine and increased levels of glycerophosphocholine. This spectral profile was confirmed by ex vivo analysis of tumor extracts, and it was also observed in human surgical biopsies of IDH1-mutated tumors by (31)P high-resolution magic angle spinning spectroscopy. The specificity of this profile for the IDH1-R132H mutation was established by in vitro (31)P-NMR of extracts of cells overexpressing IDH1 or IDH1-R132H. Overall, our results provide evidence that the IDH1-R132H mutation alters phospholipid metabolism in gliomas involving phosphoethanolamine and glycerophosphocholine. These new noninvasive biomarkers can assist in the identification of the mutation and in research toward novel treatments that target aberrant metabolism in IDH1-mutant glioma.

Impacts of MR spectroscopic imaging on glioma patient management.

Magnetic resonance (MR) modalities are routine imaging tools in the diagnosis and management of gliomas. MR spectroscopic imaging (MRSI), which relies on the metabolic characteristics of tissues, has been developed to accelerate the understanding of gliomas and to aid in effective clinical decision making and development of targeted therapies. In this review, the potentials and practical challenges to frequently use this technique in clinical management of gliomas are discussed. The applications of new biomarkers detectable by MRSI in differential glioma diagnosis, pre- and post-treatment evaluations, and neurosurgery are also addressed.