The value of arterial spin labelling (ASL) perfusion MRI in the assessment of post-treatment progression in adult glioma: A systematic review and meta-analysis.

Background: The distinction between viable tumor and therapy-induced changes is crucial for the clinical management of patients with gliomas. This study aims to quantitatively assess the efficacy of arterial spin labeling (ASL) biomarkers, including relative cerebral blood flow (rCBF) and absolute cerebral blood flow (CBF), for the discrimination of progressive disease (PD) and treatment-related effects. Methods: Eight articles were included in the synthesis after searching the literature systematically. Data have been extracted and a meta-analysis using the random-effect model was subsequently carried out. Diagnostic accuracy assessment was also performed. Results: This study revealed that there is a significant difference in perfusion measurements between groups with PD and therapy-induced changes. The rCBF yielded a standardized mean difference (SMD) of 1.25 [95% CI 0.75, 1.75] (p < .00001). The maximum perfusion indices (rCBFmax and CBFmax) both showed equivalent discriminatory ability, with SMD of 1.35 [95% CI 0.78, 1.91] (p < .00001) and 1.56 [95% CI 0.79, 2.33] (p < .0001), respectively. Similarly, accuracy estimates were comparable among ASL-derived metrices. Pooled sensitivities [95% CI] were 0.85 [0.67, 0.94], 0.88 [0.71, 0.96], and 0.93 [0.73, 0.98], and pooled specificities [95% CI] were 0.83 [0.71, 0.91], 0.83 [0.67, 0.92], 0.84 [0.67, 0.93], for rCBF, rCBFmax and CBFmax, respectively. Corresponding HSROC area under curve (AUC) [95% CI] were 0.90 [0.87, 0.92], 0.92 [0.89, 0.94], and 0.93 [0.90, 0.95]. Conclusion: These results suggest that ASL quantitative biomarkers, particularly rCBFmax and CBFmax, have the potential to discriminate between glioma progression and therapy-induced changes.

Current state and guidance on arterial spin labeling perfusion MRI in clinical neuroimaging.

This article focuses on clinical applications of arterial spin labeling (ASL) and is part of a wider effort from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group to update and expand on the recommendations provided in the 2015 ASL consensus paper. Although the 2015 consensus paper provided general guidelines for clinical applications of ASL MRI, there was a lack of guidance on disease-specific parameters. Since that time, the clinical availability and clinical demand for ASL MRI has increased. This position paper provides guidance on using ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative disease, seizures/epilepsy, and pediatric neuroradiology applications, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications in which ASL provides unique information essential for making the diagnosis. This guidance is intended for anyone interested in using ASL in a routine clinical setting (i.e., on a single-subject basis rather than in cohort studies) building on the previous ASL consensus review.

Clinical indications and acquisition protocol for the use of dynamic contrast-enhanced MRI in head and neck cancer squamous cell carcinoma: recommendations from an expert panel.

BACKGROUND: The clinical role of perfusion-weighted MRI (PWI) in head and neck squamous cell carcinoma (HNSCC) remains to be defined. The aim of this study was to provide evidence-based recommendations for the use of PWI sequence in HNSCC with regard to clinical indications and acquisition parameters. METHODS: Public databases were searched, and selected papers evaluated applying the Oxford criteria 2011. A questionnaire was prepared including statements on clinical indications of PWI as well as its acquisition technique and submitted to selected panelists who worked in anonymity using a modified Delphi approach. Each panelist was asked to rate each statement using a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). Statements with scores equal or inferior to 5 assigned by at least two panelists were revised and re-submitted for the subsequent Delphi round to reach a final consensus. RESULTS: Two Delphi rounds were conducted. The final questionnaire consisted of 6 statements on clinical indications of PWI and 9 statements on the acquisition technique of PWI. Four of 19 (21%) statements obtained scores equal or inferior to 5 by two panelists, all dealing with clinical indications. The Delphi process was considered concluded as reasons entered by panelists for lower scores were mainly related to the lack of robust evidence, so that no further modifications were suggested. CONCLUSIONS: Evidence-based recommendations on the use of PWI have been provided by an independent panel of experts worldwide, encouraging a standardized use of PWI across university and research centers to produce more robust evidence.

Standardised lesion segmentation for imaging biomarker quantitation: a consensus recommendation from ESR and EORTC.

BACKGROUND: Lesion/tissue segmentation on digital medical images enables biomarker extraction, image-guided therapy delivery, treatment response measurement, and training/validation for developing artificial intelligence algorithms and workflows. To ensure data reproducibility, criteria for standardised segmentation are critical but currently unavailable. METHODS: A modified Delphi process initiated by the European Imaging Biomarker Alliance (EIBALL) of the European Society of Radiology (ESR) and the European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group was undertaken. Three multidisciplinary task forces addressed modality and image acquisition, segmentation methodology itself, and standards and logistics. Devised survey questions were fed via a facilitator to expert participants. The 58 respondents to Round 1 were invited to participate in Rounds 2-4. Subsequent rounds were informed by responses of previous rounds. RESULTS/CONCLUSIONS: Items with ≥ 75% consensus are considered a recommendation. These include system performance certification, thresholds for image signal-to-noise, contrast-to-noise and tumour-to-background ratios, spatial resolution, and artefact levels. Direct, iterative, and machine or deep learning reconstruction methods, use of a mixture of CE marked and verified research tools were agreed and use of specified reference standards and validation processes considered essential. Operator training and refreshment were considered mandatory for clinical trials and clinical research. Items with a 60-74% agreement require reporting (site-specific accreditation for clinical research, minimal pixel number within lesion segmented, use of post-reconstruction algorithms, operator training refreshment for clinical practice). Items with ≤ 60% agreement are outside current recommendations for segmentation (frequency of system performance tests, use of only CE-marked tools, board certification of operators, frequency of operator refresher training). Recommendations by anatomical area are also specified.

Multidelay ASL of the pediatric brain.

Arterial spin labeling (ASL) is a powerful noncontrast MRI technique for evaluation of cerebral blood flow (CBF). A key parameter in single-delay ASL is the choice of postlabel delay (PLD), which refers to the timing between the labeling of arterial free water and measurement of flow into the brain. Multidelay ASL (MDASL) utilizes several PLDs to improve the accuracy of CBF calculations using arterial transit time (ATT) correction. This approach is particularly helpful in situations where ATT is unknown, including young subjects and slow-flow conditions. In this article, we discuss the technical considerations for MDASL, including labeling techniques, quantitative metrics, and technical artefacts. We then provide a practical summary of key clinical applications with real-life imaging examples in the pediatric brain, including stroke, vasculopathy, hypoxic-ischemic injury, epilepsy, migraine, tumor, infection, and metabolic disease.

What do we know about dynamic glucose-enhanced (DGE) MRI and how close is it to the clinics? Horizon 2020 GLINT consortium report.

Cancer is one of the most devastating diseases that the world is currently facing, accounting for 10 million deaths in 2020 (WHO). In the last two decades, advanced medical imaging has played an ever more important role in the early detection of the disease, as it increases the chances of survival and the potential for full recovery. To date, dynamic glucose-enhanced (DGE) MRI using glucose-based chemical exchange saturation transfer (glucoCEST) has demonstrated the sensitivity to detect both D-glucose and glucose analogs, such as 3-oxy-methyl-D-glucose (3OMG) uptake in tumors. As one of the recent international efforts aiming at pushing the boundaries of translation of the DGE MRI technique into clinical practice, a multidisciplinary team of eight partners came together to form the "glucoCEST Imaging of Neoplastic Tumors (GLINT)" consortium, funded by the Horizon 2020 European Commission. This paper summarizes the progress made to date both by these groups and others in increasing our knowledge of the underlying mechanisms related to this technique as well as translating it into clinical practice.

CEST MRI provides amide/amine surrogate biomarkers for treatment-naïve glioma sub-typing.

PURPOSE: Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations. METHODS: Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (B1rms = 2µT, Tsat = 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3-4 ppm, amines: 1.5-2.5 ppm, amide/amine ratio) were calculated with two models: 'asymmetry-based' (AB) and 'fluid-suppressed' (FS). The presence of T2/FLAIR mismatch was noted. RESULTS: IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19qcodel (p < 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (p < 0.0045) and from IDH-mutant_1p/19qret (p < 0.021). IDH-mutant_1p/19qret had higher amides and amines than IDH-mutant_1p/19qcodel (p < 0.035). IDH-mutant_1p/19qret with AB/FS mismatch had higher amines than IDH-mutant_1p/19qret without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19qret, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (p = 0.014). CONCLUSIONS: CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance.

Planning of gamma knife radiosurgery (GKR) for brain arteriovenous malformations using triple magnetic resonance angiography (triple-MRA).

PURPOSE: Intra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to evaluate whether a combination of three Magnetic Resonance Angiography sequences (triple-MRA) could be used for delineation of brain AVMs for Gamma Knife Radiosurgery (GKR). METHODS: Fifteen patients undergoing DSA for GKR targeting of brain AVMs also underwent triple-MRA: 4D Arterial Spin Labelling based angiography (ASL-MRA), Contrast-Enhanced Time-Resolved MRA (CE-MRA) and High Definition post-contrast Time-Of-Flight angiography (HD-TOF). The arterial phase of the AVM nidus was delineated on triple-MRA by an interventional neuroradiologist and a consultant neurosurgeon (triple-MRA volume). Triple-MRA volumes were compared to AVM targets delineated by the clinical team for delivery of GKR using the current planning paradigm, i.e., stereotactic DSA and volumetric MRI (DSA volume). Difference in size, degree of inclusion (DI) and concordance index (CcI) between DSA and triple-MRA volumes are reported. RESULTS: AVM target volumes delineated on triple-MRA were on average 9.8% smaller than DSA volumes (95%CI:5.6-13.9%; SD:7.14%; p = .003). DI of DSA volume in triple-MRA volume was on average 73.5% (95%CI:71.2-76; range: 65-80%). The mean percentage of triple-MRA volume not included on DSA volume was 18% (95%CI:14.7-21.3; range: 7-30%). CONCLUSION: The technical feasibility of using triple-MRA for visualisation and delineation of brain AVMs for GKR planning has been demonstrated. Tighter and more precise delineation of AVM target volumes could be achieved by using triple-MRA for radiosurgery targeting. However, further research is required to ascertain the impact this may have in obliteration rates and side effects.

Repeatability of perfusion measurements in adult gliomas using pulsed and pseudo-continuous arterial spin labelling MRI.

OBJECTIVES: To investigate the repeatability of perfusion measures in gliomas using pulsed- and pseudo-continuous-arterial spin labelling (PASL, PCASL) techniques, and evaluate different regions-of-interest (ROIs) for relative tumour blood flow (rTBF) normalisation. MATERIALS AND METHODS: Repeatability of cerebral blood flow (CBF) was measured in the Contralateral Normal Appearing Hemisphere (CNAH) and in brain tumours (aTBF). rTBF was normalised using both large/small ROIs from the CNAH. Repeatability was evaluated with intra-class-correlation-coefficient (ICC), Within-Coefficient-of-Variation (WCoV) and Coefficient-of-Repeatability (CR). RESULTS: PASL and PCASL demonstrated high reliability (ICC > 0.9) for CNAH-CBF, aTBF and rTBF. PCASL demonstrated a more stable signal-to-noise ratio (SNR) with a lower WCoV of the SNR than that of PASL (10.9-42.5% vs. 12.3-29.2%). PASL and PCASL showed higher WCoV in aTBF and rTBF than in CNAH CBF in WM and GM but not in the caudate, and higher WCoV for rTBF than for aTBF when normalised using a small ROI (PASL 8.1% vs. 4.7%, PCASL 10.9% vs. 7.9%, respectively). The lowest CR was observed for rTBF normalised with a large ROI. DISCUSSION: PASL and PCASL showed similar repeatability for the assessment of perfusion parameters in patients with primary brain tumours as previous studies based on volunteers. Both methods displayed reasonable WCoV in the tumour area and CNAH. PCASL's more stable SNR in small areas (caudate) is likely to be due to the longer post-labelling delays.

Development, validation, qualification, and dissemination of quantitative MR methods: Overview and recommendations by the ISMRM quantitative MR study group.

On behalf of the International Society for Magnetic Resonance in Medicine (ISMRM) Quantitative MR Study Group, this article provides an overview of considerations for the development, validation, qualification, and dissemination of quantitative MR (qMR) methods. This process is framed in terms of two central technical performance properties, i.e., bias and precision. Although qMR is confounded by undesired effects, methods with low bias and high precision can be iteratively developed and validated. For illustration, two distinct qMR methods are discussed throughout the manuscript: quantification of liver proton-density fat fraction, and cardiac T1 . These examples demonstrate the expansion of qMR methods from research centers toward widespread clinical dissemination. The overall goal of this article is to provide trainees, researchers, and clinicians with essential guidelines for the development and validation of qMR methods, as well as an understanding of necessary steps and potential pitfalls for the dissemination of quantitative MR in research and in the clinic.

GLINT: GlucoCEST in neoplastic tumors at 3 T-clinical results of GlucoCEST in gliomas.

OBJECTIVE: Clinical relevance of dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) imaging has mostly been demonstrated at ultra-high field (UHF) due to low effect size. Results of a cohort study at clinical field strength are shown herein. MATERIALS AND METHODS: Motion and field inhomogeneity corrected T1ρ-based DGE (DGE⍴) images were acquired before, during and after a D-glucose injection with 6.3 s temporal resolution to detect accumulation in the brain. Six glioma patients with clear blood-brain barrier (BBB) leakage, two glioma patients with suspected BBB leakage, and three glioma patients without BBB leakage were scanned at 3 T. RESULTS: In high-grade gliomas with BBB leakage, D-glucose uptake could be detected in the gadolinium (Gd) enhancing region as well as in the tumor necrosis with a maximum increase of ∆DGE⍴ around 0.25%, whereas unaffected white matter did not show any significant DGE⍴ increase. Glioma patients without Gd enhancement showed no detectable DGE⍴ effect within the tumor. CONCLUSION: First application of DGE⍴ in a patient cohort shows an association between BBB leakage and DGE signal irrespective of the tumor grade. This indicates that glucoCEST corresponds more to the disruptions of BBB with Gd uptake than to the molecular tumor profile or tumor grading.

Convergent and Discriminant Validity of Default Mode Network and Limbic Network Perfusion in Amnestic Mild Cognitive Impairment Patients.

BACKGROUND: Previous studies reported default mode network (DMN) and limbic network (LIN) brain perfusion deficits in patients with amnestic mild cognitive impairment (aMCI), frequently a prodromal stage of Alzheimer's disease (AD). However, the validity of these measures as AD markers has not yet been tested using MRI arterial spin labeling (ASL). OBJECTIVE: To investigate the convergent and discriminant validity of DMN and LIN perfusion in aMCI. METHODS: We collected core AD markers (amyloid-ß 42 [Aß42], phosphorylated tau 181 levels in cerebrospinal fluid [CSF]), neurodegenerative (hippocampal volumes and CSF total tau), vascular (white matter hyperintensities), genetic (apolipoprotein E [APOE] status), and cognitive features (memory functioning on Paired Associate Learning test [PAL]) in 14 aMCI patients. Cerebral blood flow (CBF) was extracted from DMN and LIN using ASL and correlated with AD features to assess convergent validity. Discriminant validity was assessed carrying out the same analysis with AD-unrelated features, i.e., somatomotor and visual networks' perfusion, cerebellar volume, and processing speed. RESULTS: Perfusion was reduced in the DMN (F = 5.486, p = 0.039) and LIN (F = 12.678, p = 0.004) in APOE ɛ4 carriers compared to non-carriers. LIN perfusion correlated with CSF Aß42 levels (r = 0.678, p = 0.022) and memory impairment (PAL, number of errors, r = -0.779, p = 0.002). No significant correlation was detected with tau, neurodegeneration, and vascular features, nor with AD-unrelated features. CONCLUSION: Our results support the validity of DMN and LIN ASL perfusion as AD markers in aMCI, indicating a significant correlation between CBF and amyloidosis, APOE ɛ4, and memory impairment.

Serial blood cytokine and chemokine mRNA and microRNA over 48 h are insult specific in a piglet model of inflammation-sensitized hypoxia-ischaemia.

BACKGROUND: Exposure to inflammation exacerbates injury in neonatal encephalopathy (NE). We hypothesized that brain biomarker mRNA, cytokine mRNA and microRNA differentiate inflammation (E. coli LPS), hypoxia (Hypoxia), and inflammation-sensitized hypoxia (LPS+Hypoxia) in an NE piglet model. METHODS: Sixteen piglets were randomized: (i) LPS 2 µg/kg bolus; 1 µg/kg infusion (LPS; n = 5), (ii) Saline with hypoxia (Hypoxia; n = 6), (iii) LPS commencing 4 h pre-hypoxia (LPS+Hypoxia; n = 5). Total RNA was acquired at baseline, 4 h after LPS and 1, 3, 6, 12, 24, 48 h post-insult (animals euthanized at 48 h). Quantitative PCR was performed for cytokines (IL1A, IL6, CXCL8, IL10, TNFA) and brain biomarkers (ENO2, UCHL1, S100B, GFAP, CRP, BDNF, MAPT). MicroRNA was detected using GeneChip (Affymetrix) microarrays. Fold changes from baseline were compared between groups and correlated with cell death (TUNEL) at 48 h. RESULTS: Within 6 h post-insult, we observed increased IL1A, CXCL8, CCL2 and ENO2 mRNA in LPS+Hypoxia and LPS compared to Hypoxia. IL10 mRNA differentiated all groups. Four microRNAs differentiated LPS+Hypoxia and Hypoxia: hsa-miR-23a, 27a, 31-5p, 193-5p. Cell death correlated with TNFA (R = 0.69; p < 0.01) at 1-3 h and ENO2 (R = -0.69; p = 0.01) at 48 h. CONCLUSIONS: mRNA and miRNA differentiated hypoxia from inflammation-sensitized hypoxia within 6 h in a piglet model. This information may inform human studies to enable triage for tailored neuroprotection in NE. IMPACT: Early stratification of infants with neonatal encephalopathy is key to providing tailored neuroprotection. IL1A, CXCL8, IL10, CCL2 and NSE mRNA are promising biomarkers of inflammation-sensitized hypoxia. IL10 mRNA levels differentiated all three pathological states; fold changes from baseline was the highest in LPS+Hypoxia animals, followed by LPS and Hypoxia at 6 h. miR-23, -27, -31-5p and -193-5p were significantly upregulated within 6 h of a hypoxia insult. Functional analysis highlighted the diverse roles of miRNA in cellular processes.

Human umbilical cord mesenchymal stromal cells as an adjunct therapy with therapeutic hypothermia in a piglet model of perinatal asphyxia.

BACKGROUND: With therapeutic hypothermia (HT) for neonatal encephalopathy, disability rates are reduced, but not all babies benefit. Pre-clinical rodent studies suggest mesenchymal stromal cells (MSCs) augment HT protection. AIMS: The authors studied the efficacy of intravenous (IV) or intranasal (IN) human umbilical cord-derived MSCs (huMSCs) as adjunct therapy to HT in a piglet model. METHODS: A total of 17 newborn piglets underwent transient cerebral hypoxia-ischemia (HI) and were then randomized to (i) HT at 33.5°C 1-13 h after HI (n = 7), (ii) HT+IV huMSCs (30 × 106 cells) at 24 h and 48 h after HI (n = 5) or (iii) HT+IN huMSCs (30 × 106 cells) at 24 h and 48 h after HI (n = 5). Phosphorus-31 and hydrogen-1 magnetic resonance spectroscopy (MRS) was performed at 30 h and 72 h and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells and oligodendrocytes quantified. In two further piglets, 30 × 106 IN PKH-labeled huMSCs were administered. RESULTS: HI severity was similar between groups. Amplitude-integrated electroencephalogram (aEEG) recovery was more rapid for HT+IN huMSCs compared with HT from 25 h to 42 h and 49 h to 54 h (P ≤ 0.05). MRS phosphocreatine/inorganic phosphate was higher on day 2 in HT+IN huMSCs than HT (P = 0.035). Comparing HT+IN huMSCs with HT and HT+IV huMSCs, there were increased OLIG2 counts in hippocampus (P = 0.011 and 0.018, respectively), internal capsule (P = 0.013 and 0.037, respectively) and periventricular white matter (P = 0.15 for IN versus IV huMSCs). Reduced TUNEL-positive cells were seen in internal capsule with HT+IN huMSCs versus HT (P = 0.05). PKH-labeled huMSCs were detected in the brain 12 h after IN administration. CONCLUSIONS: After global HI, compared with HT alone, the authors saw beneficial effects of HT+IN huMSCs administered at 24 h and 48 h (30 × 106 cells/kg total dose) based on more rapid aEEG recovery, improved 31P MRS brain energy metabolism and increased oligodendrocyte survival at 72 h.

Endogenous Chemical Exchange Saturation Transfer MRI for the Diagnosis and Therapy Response Assessment of Brain Tumors: A Systematic Review.

Purpose: To generate a narrative synthesis of published data on the use of endogenous chemical exchange saturation transfer (CEST) MRI in brain tumors. Materials and Methods: A systematic database search (PubMed, Ovid Embase, Cochrane Library) was used to collate eligible studies. Two researchers independently screened publications according to predefined exclusion and inclusion criteria, followed by comprehensive data extraction. All included studies were subjected to a bias risk assessment using the Quality Assessment of Diagnostic Accuracy Studies tool. Results: The electronic database search identified 430 studies, of which 36 fulfilled the inclusion criteria. The final selection of included studies was categorized into five groups as follows: grading gliomas, 19 studies (area under the receiver operating characteristic curve [AUC], 0.500-1.000); predicting molecular subtypes of gliomas, five studies (AUC, 0.610-0.920); distinction of different brain tumor types, seven studies (AUC, 0.707-0.905); therapy response assessment, three studies (AUC not given); and differentiating recurrence from treatment-related changes, five studies (AUC, 0.880-0.980). A high bias risk was observed in a substantial proportion of studies. Conclusion: Endogenous CEST MRI offers valuable, potentially unique information in brain tumors, but its diagnostic accuracy remains incompletely known. Further research is required to assess the method's role in support of molecular genetic diagnosis, to investigate its use in the posttreatment phase, and to compare techniques with a view to standardization.Keywords: Brain/Brain Stem, MR-Imaging, Neuro-OncologySupplemental material is available for this article.© RSNA, 2020.

Challenges in glucoCEST MR body imaging at 3 Tesla.

BACKGROUND: The aim of this study was to translate dynamic glucose enhancement (DGE) body magnetic resonance imaging (MRI) based on the glucose chemical exchange saturation transfer (glucoCEST) signal to a 3 T clinical field strength. METHODS: An infusion protocol for intravenous (i.v.) glucose was optimised using a hyperglycaemic clamp to maximise the chances of detecting exchange-sensitive MRI signal. Numerical simulations were performed to define the optimum parameters for glucoCEST measurements with consideration to physiological conditions. DGE images were acquired for patients with lymphomas and prostate cancer injected i.v. with 20% glucose. RESULTS: The optimised hyperglycaemic clamp infusion based on the DeFronzo method demonstrated higher efficiency and stability of glucose delivery as compared to manual determination of glucose infusion rates. DGE signal sensitivity was found to be dependent on T2, B1 saturation power and integration range. Our results show that motion correction and B0 field inhomogeneity correction are crucial to avoid mistaking signal changes for a glucose response while field drift is a substantial contributor. However, after B0 field drift correction, no significant glucoCEST signal enhancement was observed in tumour regions of all patients in vivo. CONCLUSIONS: Based on our simulated and experimental results, we conclude that glucose-related signal remains elusive at 3 T in body regions, where physiological movements and strong effects of B1 + and B0 render the originally small glucoCEST signal difficult to detect.

Diagnostic accuracy of dynamic contrast-enhanced perfusion MRI in stratifying gliomas: A systematic review and meta-analysis.

BACKGROUND: T1-weighted dynamic contrast-enhanced (DCE) perfusion magnetic resonance imaging (MRI) has been broadly utilized in the evaluation of brain tumors. We aimed at assessing the diagnostic accuracy of DCE-MRI in discriminating between low-grade gliomas (LGGs) and high-grade gliomas (HGGs), between tumor recurrence and treatment-related changes, and between primary central nervous system lymphomas (PCNSLs) and HGGs. METHODS: We performed this study based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis of Diagnostic Test Accuracy Studies criteria. We systematically surveyed studies evaluating the diagnostic accuracy of DCE-MRI for the aforementioned entities. Meta-analysis was conducted with the use of a random effects model. RESULTS: Twenty-seven studies were included after screening of 2945 possible entries. We categorized the eligible studies into three groups: those utilizing DCE-MRI to differentiate between HGGs and LGGs (14 studies, 546 patients), between recurrence and treatment-related changes (9 studies, 298 patients) and between PCNSLs and HGGs (5 studies, 224 patients). The pooled sensitivity, specificity, and area under the curve for differentiating HGGs from LGGs were 0.93, 0.90, and 0.96, for differentiating tumor relapse from treatment-related changes were 0.88, 0.86, and 0.89, and for differentiating PCNSLs from HGGs were 0.78, 0.81, and 0.86, respectively. CONCLUSIONS: Dynamic contrast-enhanced-Magnetic resonance imaging is a promising noninvasive imaging method that has moderate or high accuracy in stratifying gliomas. DCE-MRI shows high diagnostic accuracy in discriminating between HGGs and their low-grade counterparts, and moderate diagnostic accuracy in discriminating recurrent lesions and treatment-related changes as well as PCNSLs and HGGs.

Validated imaging biomarkers as decision-making tools in clinical trials and routine practice: current status and recommendations from the EIBALL* subcommittee of the European Society of Radiology (ESR).

Observer-driven pattern recognition is the standard for interpretation of medical images. To achieve global parity in interpretation, semi-quantitative scoring systems have been developed based on observer assessments; these are widely used in scoring coronary artery disease, the arthritides and neurological conditions and for indicating the likelihood of malignancy. However, in an era of machine learning and artificial intelligence, it is increasingly desirable that we extract quantitative biomarkers from medical images that inform on disease detection, characterisation, monitoring and assessment of response to treatment. Quantitation has the potential to provide objective decision-support tools in the management pathway of patients. Despite this, the quantitative potential of imaging remains under-exploited because of variability of the measurement, lack of harmonised systems for data acquisition and analysis, and crucially, a paucity of evidence on how such quantitation potentially affects clinical decision-making and patient outcome. This article reviews the current evidence for the use of semi-quantitative and quantitative biomarkers in clinical settings at various stages of the disease pathway including diagnosis, staging and prognosis, as well as predicting and detecting treatment response. It critically appraises current practice and sets out recommendations for using imaging objectively to drive patient management decisions.

Effect of Liposomal Encapsulation on the Chemical Exchange Properties of Diamagnetic CEST Agents.

Exogenous chemical exchange saturation transfer (CEST) contrast agents such as glucose or 2-deoxy-d-glucose (2-DG) have shown high sensitivities and significant potential for monitoring glucose uptake in tumors with MRI. Here, we show that liposome encapsulation of such agents can be exploited to enhance the CEST signal by reducing the overall apparent exchange rate. We have developed a concise analytical model to describe the liposomal contrast dependence on several parameters such as pH, temperature, irradiation amplitude, and intraliposomal water content. This is the first study in which a model has been constructed to measure the exchange properties of diamagnetic CEST agents encapsulated inside liposomes. Experimentally measured exchange rates of glucose and 2-DG in the liposomal system were found to be reduced due to the intermembrane exchange between the intra- and extraliposomal compartments because of restrictions in water transfer imposed by the lipid membrane. These new theoretical and experimental findings will benefit applications of diamagnetic liposomes to image biological processes. In addition, combining this analytical model with measurements of the CEST signal enhancement using liposomes as a model membrane system is an important new general technique for studying membrane permeability.