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Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.
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Encéfalo , Circulação Cerebrovascular , Marcadores de Spin , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Imagem de PerfusãoRESUMO
OBJECTIVE: Intraoperative Doppler ultrasound imaging of human brain vasculature is an emerging neuro-imaging modality that offers vascular brain mapping with unprecedented spatiotemporal resolution. At present, however, access to the human brain using Doppler Ultrasound is only possible in this intraoperative context, posing a significant challenge for validation of imaging techniques. This challenge necessitates the development of realistic flow phantoms outside of the neurosurgical operating room as external platforms for testing hardware and software. An ideal ultrasound flow phantom should provide reference-like values in standardized topologies such as a slanted pipe, and allow for measurements in structures closely resembling vascular morphology of actual patients. Additionally, the phantom should be compatible with other clinical cerebrovascular imaging modalities. To meet these criteria, we developed and validated a versatile, multimodal MRI- and ultrasound Doppler phantom. METHODS: Our approach incorporates the latest advancements in phantom research using tissue-mimicking material and 3D-printing with water-soluble resin to create wall-less patient-specific lumens, compatible for ultrasound and MRI. RESULTS: We successfully produced three distinct phantoms: a slanted pipe, a y-shape phantom representing a bifurcating vessel and an arteriovenous malformation (AVM) derived from clinical Digital Subtraction Angiography (DSA)-data of the brain. We present 3D ultrafast power Doppler imaging results from these phantoms, demonstrating their ability to mimic complex flow patterns as observed in the human brain. Furthermore, we showcase the compatibility of our phantom with Magnetic Resonance Imaging (MRI). CONCLUSION: We developed an MRI- and Doppler Ultrasound-compatible flow-phantom using customizable, water-soluble resin prints ranging from geometrical forms to patient-specific vasculature.
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Imageamento por Ressonância Magnética , Imagens de Fantasmas , Ultrassonografia Doppler , Humanos , Imageamento por Ressonância Magnética/métodos , Ultrassonografia Doppler/métodos , Circulação Cerebrovascular/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Desenho de EquipamentoRESUMO
BACKGROUND: We aimed to describe the microvascular features of three types of adult-type diffuse glioma by comparing dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) with intraoperative high-frame-rate ultrafast Doppler ultrasound. METHODS: Case series of seven patients with primary brain tumours underwent both DSC perfusion MRI and intra-operative high-frame-rate ultrafast Doppler ultrasound. From the ultrasound images, three-dimensional vessel segmentation was obtained of the tumour vascular bed. Relative cerebral blood volume (rCBV) maps were generated with leakage correction and normalised to the contralateral normal-appearing white matter. From tumour histograms, median, mean, and maximum rCBV ratios were extracted. RESULTS: Low-grade gliomas (LGGs) showed lower perfusion than high-grade gliomas (HGGs), as expected. Within the LGG subgroup, oligodendroglioma showed higher perfusion than astrocytoma. In HGG, the median rCBV ratio for glioblastoma was 3.1 while astrocytoma grade 4 showed low perfusion with a median rCBV of 1.2. On the high-frame-rate ultrafast Doppler ultrasound images, all tumours showed a range of rich and organised vascular networks with visually apparent abnormal vessels, even in LGG. CONCLUSIONS: This unique case series revealed in vivo insights about the microvascular architecture in both LGGs and HGGs. Ultrafast Doppler ultrasound revealed rich vascularisation, also in tumours with low perfusion at DSC MRI. These findings warrant further investigations using advanced MRI postprocessing, in particular for characterising adult-type diffuse glioma. RELEVANCE STATEMENT: Our findings challenge the current assumption behind the estimation of relative cerebral blood volume that the distribution of blood vessels in a voxel is random. KEY POINTS: ⢠Ultrafast Doppler ultrasound revealed rich vascularity irrespective of perfusion dynamic susceptibility contrast MRI state. ⢠Rich and organised vascularisation was also observed even in low-grade glioma. ⢠These findings challenge the assumptions for cerebral blood volume estimation with MRI.
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Astrocitoma , Neoplasias Encefálicas , Glioma , Adulto , Humanos , Angiografia por Ressonância Magnética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Glioma/diagnóstico por imagem , Glioma/cirurgia , Imageamento por Ressonância Magnética/métodos , Astrocitoma/patologia , Ultrassonografia Doppler , Perfusão , Microvasos/patologiaRESUMO
OBJECTIVE: Presurgical differentiation between astrocytomas and oligodendrogliomas remains an unresolved challenge in neuro-oncology. This research aims to provide a comprehensive understanding of each tumor's DSC-PWI signatures, evaluate the discriminative capacity of cerebral blood volume (CBV) and percentage of signal recovery (PSR) percentile values, and explore the synergy of CBV and PSR combination for pre-surgical differentiation. METHODS: Patients diagnosed with grade 2 and 3 IDH-mutant astrocytomas and IDH-mutant 1p19q-codeleted oligodendrogliomas were retrospectively retrieved (2010-2022). 3D segmentations of each tumor were conducted, and voxel-level CBV and PSR were extracted to compute mean, minimum, maximum, and percentile values. Statistical comparisons were performed using the Mann-Whitney U test and the area under the receiver operating characteristic curve (AUC-ROC). Lastly, the five most discriminative variables were combined for classification with internal cross-validation. RESULTS: The study enrolled 52 patients (mean age 45-year-old, 28 men): 28 astrocytomas and 24 oligodendrogliomas. Oligodendrogliomas exhibited higher CBV and lower PSR than astrocytomas across all metrics (e.g., mean CBV = 2.05 and 1.55, PSR = 0.68 and 0.81 respectively). The highest AUC-ROCs and the smallest p values originated from CBV and PSR percentiles (e.g., PSRp70 AUC-ROC = 0.84 and p value = 0.0005, CBVp75 AUC-ROC = 0.8 and p value = 0.0006). The mean, minimum, and maximum values yielded lower results. Combining the best five variables (PSRp65, CBVp70, PSRp60, CBVp75, and PSRp40) achieved a mean AUC-ROC of 0.87 for differentiation. CONCLUSIONS: Oligodendrogliomas exhibit higher CBV and lower PSR than astrocytomas, traits that are emphasized when considering percentiles rather than mean or extreme values. The combination of CBV and PSR percentiles results in promising classification outcomes. CLINICAL RELEVANCE STATEMENT: The combination of histogram-derived percentile values of cerebral blood volume and percentage of signal recovery from DSC-PWI enhances the presurgical differentiation between astrocytomas and oligodendrogliomas, suggesting that incorporating these metrics into clinical practice could be beneficial. KEY POINTS: ⢠The unsupervised selection of percentile values for cerebral blood volume and percentage of signal recovery enhances presurgical differentiation of astrocytomas and oligodendrogliomas. ⢠Oligodendrogliomas exhibit higher cerebral blood volume and lower percentage of signal recovery than astrocytomas. ⢠Cerebral blood volume and percentage of signal recovery combined provide a broader perspective on tumor vasculature and yield promising results for this preoperative classification.
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Astrocitoma , Neoplasias Encefálicas , Volume Sanguíneo Cerebral , Isocitrato Desidrogenase , Oligodendroglioma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Astrocitoma/diagnóstico por imagem , Astrocitoma/cirurgia , Astrocitoma/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/genética , Diagnóstico Diferencial , Isocitrato Desidrogenase/genética , Imageamento por Ressonância Magnética/métodos , Mutação , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Dynamic glucose-enhanced (DGE) chemical exchange saturation transfer (CEST) has the potential to characterize glucose metabolism in brain metastases. Since the effect size of DGE CEST is small at 3 T (< 1%), measurements of signal-to-noise ratios are challenging. To improve DGE detection, we developed an acquisition pipeline and extended image analysis for DGE CEST on a hybrid 3-T positron emission tomography/magnetic resonance imaging system. METHODS: This cross-sectional study was conducted after local ethical approval. Static Z-spectra (from -100 to 100 ppm) were acquired to compare the use of 1.2 versus 2 ppm to calculate static glucose-enhanced (glucoCEST) maps in 10 healthy volunteers before and after glucose infusion. Dynamic CEST images were acquired during glucose infusion. Image analysis was optimized using motion correction, dynamic B0 correction, and principal component analysis (PCA) to improve the detection of DGE CEST in the sagittal sinus, cerebrospinal fluid, and grey and white matter. The developed DGE CEST pipeline was applied to four patients diagnosed with brain metastases. RESULTS: GlucoCEST was strongest in healthy tissues at 2 ppm. Correcting for motion, B0, and use of PCA locally improved DGE maps. A larger contrast between healthy tissues and enhancing regions in brain metastases was found when dynamic B0 correction and PCA denoising were applied. CONCLUSION: We demonstrated the feasibility of DGE CEST with our developed acquisition and analysis pipeline at 3 T in patients with brain metastases. This work enables a direct comparison of DGE CEST to 18F-fluoro-deoxy-D-glucose positron emission tomography of glucose metabolism in patients with brain metastases. RELEVANCE STATEMENT: Contrast between brain metastasis and healthy brain tissue in DGE CEST MR images is improved by including principle component analysis and dynamic magnetic field correction during postprocessing. This approach enables the detection of increased DGE CEST signal in brain metastasis, if present. KEY POINTS: ⢠Despite the low signal-to-noise ratio, dynamic glucose-enhanced CEST MRI is feasible at 3 T. ⢠Principal component analyses and dynamic magnetic field correction improve DGE CEST MRI. ⢠DGE CEST MRI does not consequently show changes in brain metastases compared to healthy brain tissue. ⢠Increased DGE CEST MRI in brain metastases, if present, shows overlap with contrast enhancement on T1-weighted images.
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Neoplasias Encefálicas , Glucose , Humanos , Estudos Transversais , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodosRESUMO
Amide proton transfer (APT)-weighted chemical exchange saturation transfer (CEST) imaging is a recent MRI technique making its way into clinical application. In this work, we investigated whether APT-weighted CEST imaging can provide reproducible measurements across scan sessions and scanners. Within-session, between-session and between scanner reproducibility was calculated for 19 healthy volunteers and 7 patients with a brain tumor on two 3T MRI scanners. The APT-weighted CEST effect was evaluated by calculating the Lorentzian Difference (LD), magnetization transfer ratio asymmetry (MTRasym), and relaxation-compensated inverse magnetization transfer ratio (MTRREX) averaged in whole brain white matter (WM), enhancing tumor and necrosis. Within subject coefficient of variation (COV) calculations, Bland-Altman plots and mixed effect modeling were performed to assess the repeatability and reproducibility of averaged values. The group median COVs of LD APT were 0.56% (N = 19), 0.84% (N = 6), 0.80% (N = 9) in WM within-session, between-session and between-scanner respectively. The between-session COV of LD APT in enhancing tumor (N = 6) and necrotic core (N = 3) were 4.57% and 5.67%, respectively. There were no significant differences in within session, between session and between scanner comparisons of the APT effect. The COVs of LD and MTRREX were consistently lower than MTRasym in all experiments, both in healthy tissues and tumor. The repeatability and reproducibility of APT-weighted CEST was clinically acceptable across scan sessions and scanners. Although MTRasym is simple to acquire and compute and sufficient to provide robust measurement, it is beneficial to include LD and MTRREX to obtain higher reproducibility for detecting minor signal difference in different tissue types.
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Neoplasias Encefálicas , Prótons , Humanos , Amidas , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
OBJECTIVES: Arterial spin labelling (ASL) perfusion MRI is one of the available advanced MRI techniques for brain tumour surveillance. The first aim of this study was to investigate the correlation between quantitative cerebral blood flow (CBF) and non-quantitative perfusion weighted imaging (ASL-PWI) measurements. The second aim was to investigate the diagnostic accuracy of ASL-CBF and ASL-PWI measurements as well as visual assessment for identifying tumour progression. METHODS: A consecutive cohort of patients who underwent 3-T MRI surveillance containing ASL for treated brain tumours was used. ROIs were drawn in representative parts of tumours in the ASL-CBF maps and copied to the ASL-PWI. ASL-CBF ratios and ASL-PWI ratios of the tumour ROI versus normal appearing white matter (NAWM) were correlated (Pearson correlation) and AUCs were calculated to assess diagnostic accuracy. Additionally, lesions were visually classified as hypointense, isointense, or hyperintense. We calculated accuracy at two thresholds: low threshold (between hypointense-isointense) and high threshold (between isointense-hyperintense). RESULTS: A total of 173 lesions, both enhancing and non-enhancing, measured in 115 patients (93 glioma, 16 metastasis, and 6 lymphoma) showed a very high correlation of 0.96 (95% CI: 0.88-0.99) between ASL-CBF ratios and ASL-PWI ratios. AUC was 0.76 (95%CI: 0.65-0.88) for ASL-CBF ratios and 0.72 (95%CI: 0.58-0.85) for ASL-PWI ratios. Diagnostic accuracy of visual assessment for enhancing lesions was 0.72. CONCLUSION: ASL-PWI ratios and ASL-CBF ratios showed a high correlation and comparable AUCs; therefore, quantification of ASL-CBF could be omitted in these patients. Visual classification had comparable diagnostic accuracy to the ASL-PWI or ASL-CBF ratios. CLINICAL RELEVANCE STATEMENT: This study shows that CBF quantification of ASL perfusion MRI could be omitted for brain tumour surveillance and that visual assessment provides the same diagnostic accuracy. This greatly reduces the complexity of the use of ASL in routine clinical practice. KEY POINTS: ⢠Arterial spin labelling MRI for clinical brain tumour surveillance is undervalued and underinvestigated. ⢠Non-quantitative and quantitative arterial spin labelling assessments show high correlation and comparable diagnostic accuracy. ⢠Quantification of arterial spin labelling MRI could be omitted to improve daily clinical workflow.
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Neoplasias Encefálicas , Linfoma , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/patologia , Circulação Cerebrovascular/fisiologia , Marcadores de SpinRESUMO
OBJECTIVE: Monitoring brain oxygenation is critical in brain tumors, as low oxygenation influences tumor growth, pathological angiogenesis, and treatment resistance. This study examined the ability of the streamlined quantitative (sq)BOLD MRI technique to detect oxygenation changes in healthy individuals, as well as its potential application in a clinical setting. METHODS: We used the asymmetric spin echo (ASE) technique with FLAIR preparation, along with model-based Bayesian inference to quantify the reversible transverse relaxation rate (R2') and oxygen extraction fraction (OEF) across the brain at baseline and during visual stimulation in eight healthy participants at 3T; and two patients with glioma at rest only. RESULTS: Comparing sqBOLD-derived parameters between baseline and visual stimulation revealed a decrease in OEF from 0.56 ± 0.09 at baseline to 0.54 ± 0.07 at the activated state (p = 0.04, paired t test) within a functional localizer-defined volume of interest, and a decline in R2' from 6.5 ± 1.3s-1 at baseline to 6.2 ± 1.4s-1 at the activated state (p = 0.006, paired t test) in the visual cortex. CONCLUSION: The sqBOLD technique is sensitive enough to detect and quantify changes in oxygenation in the healthy brain and shows potential for integration into clinical settings to provide valuable information on oxygenation in glioma.
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Glioma , Oxigênio , Humanos , Voluntários Saudáveis , Teorema de Bayes , Encéfalo , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico por imagemRESUMO
BACKGROUND: This Phase 1 study evaluates the intra- and peritumoral administration by convection enhanced delivery (CED) of human recombinant Bone Morphogenetic Protein 4 (hrBMP4) - an inhibitory regulator of cancer stem cells (CSCs) - in recurrent glioblastoma. METHODS: In a 3 + 3 dose escalation design, over four to six days, fifteen recurrent glioblastoma patients received, by CED, one of five doses of hrBMP4 ranging from 0·5 to 18 mg. Patients were followed by periodic physical, neurological, blood testing, magnetic resonance imaging (MRI) and quality of life evaluations. The primary objective of this first-in-human study was to determine the safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of hrBMP4. Secondary objectives were to assess potential efficacy and systemic exposure to hrBMP4 upon intracerebral infusion. RESULTS: Intra- and peritumoral infusion of hrBMP4 was safe and well-tolerated. We observed no serious adverse events related to this drug. Neither MTD nor DLT were reached. Three patients had increased hrBMP4 serum levels at the end of infusion, which normalized within 4 weeks, without sign of toxicity. One patient showed partial response and two patients a complete (local) tumor response, which was maintained until the most recent follow-up, 57 and 30 months post-hrBMP4. Tumor growth was inhibited in areas permeated by hrBMP4. CONCLUSION: Local delivery of hrBMP4 in and around recurring glioblastoma is safe and well-tolerated. Three patients responded to the treatment. A complete response and long-term survival occurred in two of them. This warrants further clinical studies on this novel treatment targeting glioblastoma CSCs. TRIAL REGISTRATION: ClinicaTrials.gov identifier: NCT02869243.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Qualidade de Vida , Proteína Morfogenética Óssea 4/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Encefálicas/patologia , Dose Máxima TolerávelRESUMO
In this study, we used the vessel size imaging (VSI) MRI technique to characterize the microvasculature features of three subtypes of adult-type diffuse glioma lacking enhancement. Thirty-eight patients with confirmed non-enhancing glioma were categorized into three subtypes: Oligo (IDH-mut&1p/19q-codeleted), Astro (IDH-mut), and GBM (IDH-wt). The VSI technique provided quantitative maps of cerebral blood volume (CBV), microvasculature (µCBV), and vessel size for each patient. Additionally, tissue samples of 21 patients were histopathologically analyzed, and microvasculature features were quantified. Both MRI- and histology-derived features were compared across the three glioma subtypes with ANOVA or Kruskal-Wallis tests. Group averages of CBV, µCBV, and vessel size were significantly different between the three glioma subtypes (p < 0.01). Astro (IDH-mut) had a significantly lower CBV and µCBV compared to Oligo (IDH-mut&1p/19q-codeleted) (p = 0.004 and p = 0.001, respectively), and a higher average vessel size compared to GBM (IDH-wt) (p = 0.01). The histopathological analysis showed that GBM (IDH-wt) possessed vessels with more irregular shapes than the two other subtypes (p < 0.05). VSI provides a good insight into the microvasculature characteristics of the three adult-type glioma subtypes even when lacking enhancement. Further investigations into the specificity of VSI to differentiate glioma subtypes are thus warranted.
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Characterization of tumor microvasculature is important in tumor assessment and studying treatment response. This is possible by acquiring vascular biomarkers with magnetic resonance imaging (MRI) based on dynamic susceptibility contrast (DSC). We propose magnetic resonance vascular fingerprinting (MRVF) for hybrid echo planar imaging (HEPI) acquired during the first passage of the contrast agent (CA). The proposed approach was evaluated in patients with gliomas, and we simultaneously estimated vessel radius and relative cerebral blood volume. These parameters were also compared to the respective values estimated using the previously introduced vessel size imaging (VSI) technique. The results of both methods were found to be consistent. MRVF was also found to be robust to noise in the estimation of the parameters. DSC-HEPI-based MRVF provides characterization of microvasculature in gliomas with a short acquisition time and can be further improved in several ways to increase our understanding of tumor physiology.
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Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.
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Neoplasias Encefálicas , Glioma , Imageamento por Ressonância Magnética , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Meios de Contraste , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Período Pré-OperatórioRESUMO
Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.
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Neoplasias Encefálicas , Glioma , Humanos , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Espectroscopia de Ressonância Magnética/métodos , Imagem de Difusão por Ressonância MagnéticaRESUMO
Restoring blood flow to brain tissue at risk of infarction is essential for tissue survival and clinical outcome. We used cerebral blood flow (CBF) quantified with multiple post-labeling delay (PLD) pseudocontinuous arterial spin labeling (ASL) MRI after ischemic stroke and assessed the association between CBF and early neurological outcome. We acquired ASL with 7 PLDs at 3.0 T in large vessel occlusion stroke patients at 24 h. We quantified CBF relative to the contralateral hemisphere (rCBF) and defined hyperperfusion as a ≥30% increase and hypoperfusion as a ≥40% decrease in rCBF. We included 44 patients (median age: 70 years, median NIHSS: 13, 40 treated with endovascular thrombectomy) of whom 37 were recanalized. Hyperperfusion in ischemic core occurred in recanalized but not in non-recanalized patients (65.8% vs 0%, p = 0.006). Hypoperfusion occurred only in the latter group (0% vs 85.7%, p < 0.001). In recanalized patients, hyperperfusion was also seen in salvaged penumbra (38.9%). Higher rCBF in ischemic core (aß, -2.75 [95% CI: -4.11 to -1.40]) and salvaged penumbra (aß, -5.62 [95% CI: -9.57 to -1.68]) was associated with lower NIHSS scores at 24 h. In conclusion, hyperperfusion frequently occurs in infarcted and salvaged brain tissue following successful recanalization and early neurological outcome is positively associated with the level of reperfusion.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Idoso , Marcadores de Spin , Imageamento por Ressonância Magnética , Encéfalo , Isquemia Encefálica/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Acidente Vascular Cerebral/diagnóstico por imagemRESUMO
Perfusion MRI is promising for the assessment, prediction, and monitoring of radiation toxicity in organs at risk in head and neck cancer. Arterial spin labeling (ASL) may be an attractive alternative for conventional perfusion MRI, that does not require the administration of contrast agents. However, currently, little is known about the characteristics and performance of ASL in healthy tissues in the head and neck region. Therefore, the purpose of this study was to optimize and evaluate multidelay pseudocontinuous ASL (pCASL) for the head and neck region and to explore nominal values and measurement repeatability for the blood flow (BF), and the transit time and T1 values needed for BF quantification in healthy tissues. Twenty healthy volunteers underwent a scan session consisting of four repeats of multidelay pCASL (postlabel delays: 1000, 1632, 2479 ms). Regions of interest were defined in the parotid glands, submandibular glands, tonsils, and the cerebellum (as a reference). Nominal values of BF were calculated as the average over four repeats per volunteer. The repeatability coefficient and within-subject coefficient of repeatability (wCV) of BF were calculated. The effect of T1 (map vs. cohort average) and transit time correction on BF was investigated. The mean BF (± SE) was 55.7 ± 3.1 ml/100 g/min for the parotid glands, 41.2 ± 2.8 ml/100 g/min for the submandibular glands, and 32.3 ± 2.2 ml/100 g/min for the tonsils. The best repeatability was found in the parotid glands (wCV = 13.3%-16.1%), followed by the submandibular glands and tonsils (wCV = 20.0%-24.6%). On average, the effect of T1 and transit time correction on BF was limited, although substantial bias occurred in individual acquisitions. In conclusion, we demonstrated the feasibility of BF measurements in the head and neck region using multidelay pCASL and reported on nominal BF values, BF repeatability, the effect of T1, and transit time in various tissues in the head and neck region.
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Neoplasias de Cabeça e Pescoço , Imageamento por Ressonância Magnética , Humanos , Marcadores de Spin , Artérias , Circulação Cerebrovascular/fisiologia , Encéfalo/irrigação sanguíneaRESUMO
Cerebral hypoxia significantly impacts the progression of brain tumors and their resistance to radiotherapy. This study employed streamlined quantitative blood-oxygen-level-dependent (sqBOLD) MRI to assess the oxygen extraction fraction (OEF)-a measure of how much oxygen is being extracted from vessels, with higher OEF values indicating hypoxia. Simultaneously, we utilized vessel size imaging (VSI) to evaluate microvascular dimensions and blood volume. A cohort of ten patients, divided between those with glioma and those with brain metastases, underwent a 3 Tesla MRI scan. We generated OEF, cerebral blood volume (CBV), and vessel size maps, which guided 3-4 targeted biopsies per patient. Subsequent histological analyses of these biopsies used hypoxia-inducible factor 1-alpha (HIF-1α) for hypoxia and CD31 for microvasculature assessment, followed by a correlation analysis between MRI and histological data. The results showed that while the sqBOLD model was generally applicable to brain tumors, it demonstrated discrepancies in some metastatic tumors, highlighting the need for model adjustments in these cases. The OEF, CBV, and vessel size maps provided insights into the tumor's hypoxic condition, showing intertumoral and intratumoral heterogeneity. A significant relationship between MRI-derived measurements and histological data was only evident in the vessel size measurements (r = 0.68, p < 0.001).
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Purpose: We aimed to compare arterial spin labeling (ASL) with dynamic susceptibility contrast (DSC) enhanced perfusion MRI for the surveillance of primary and metastatic brain tumors at 3T, both in terms of lesion perfusion metrics and diagnostic accuracy. Methods: In this retrospective study, we included 115 patients, who underwent both ASL and DSC perfusion in the same 3T MRI scanning session between 1 January and 31 December 2019. ASL-derived cerebral blood flow (CBF) maps and DSC-derived relative cerebral blood volume (rCBV) maps, both uncorrected and corrected for leakage, were created with commercially available software. Lesions were identified as T2-/T2-FLAIR hyperintensity with or without contrast enhancement. Measurements were done by placing a region of interest in the visually determined area of highest perfusion, copying to the contralateral normal appearing white matter (NAWM), and then propagating to the other perfusion maps. Pearson's correlation coefficients were calculated between the CBF and rCBV ratios of tumor versus NAWM. Accuracy for diagnosing tumor progression was calculated as the area under the receiver operating characteristics (ROC) curve (AUC) for the ASL-CBF and leakage corrected DSC-rCBV ratios. Results: We identified 178 lesions, 119 with and 59 without contrast enhancement. Correlation coefficients between ASL-derived CBF versus DSC-derived rCBV ratios were 0.60-0.67 without and 0.72-0.78 with leakage correction in all lesions (n = 178); these were 0.65-0.80 in enhancing glioma (n = 80), 0.58-0.73 in non-enhancing glioma, and 0.14-0.40 in enhancing metastasis (n = 31). No significant correlation was found in enhancing (n = 8) or non-enhancing (n = 7) lymphomas. The areas under the ROC curves (AUCs) for all patients were similar for ASL and DSC (0.73-0.78), and were higher for enhancing glioma (AUC = 0.78-0.80) than for non-enhancing glioma (AUC = 0.56-0.62). In brain metastasis, the AUC was lower for ASL-derived CBF (AUC = 0.72) than for DSC-derived rCBV ratios (AUC = 0.87-0.93). Conclusion: We found that ASL and DSC have more or less the same diagnostic accuracy. Our findings suggest that ASL can be used as an alternative to DSC to measure perfusion in enhancing and non-enhancing gliomas and brain metastasis at 3T. For lymphoma, this should be further investigated in a larger population.
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Objective: Summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and highlight the latest bench-to-bedside developments. Methods: Experts in advanced MRI techniques applied to high-grade glioma treatment response assessment convened through a European framework. Current evidence regarding the potential for monitoring biomarkers in adult high-grade glioma is reviewed, and individual modalities of perfusion, permeability, and microstructure imaging are discussed (in Part 1 of two). In Part 2, we discuss modalities related to metabolism and/or chemical composition, appraise the clinic readiness of the individual modalities, and consider post-processing methodologies involving the combination of MRI approaches (multiparametric imaging) or machine learning (radiomics). Results: High-grade glioma vasculature exhibits increased perfusion, blood volume, and permeability compared with normal brain tissue. Measures of cerebral blood volume derived from dynamic susceptibility contrast-enhanced MRI have consistently provided information about brain tumor growth and response to treatment; it is the most clinically validated advanced technique. Clinical studies have proven the potential of dynamic contrast-enhanced MRI for distinguishing post-treatment related effects from recurrence, but the optimal acquisition protocol, mode of analysis, parameter of highest diagnostic value, and optimal cut-off points remain to be established. Arterial spin labeling techniques do not require the injection of a contrast agent, and repeated measurements of cerebral blood flow can be performed. The absence of potential gadolinium deposition effects allows widespread use in pediatric patients and those with impaired renal function. More data are necessary to establish clinical validity as monitoring biomarkers. Diffusion-weighted imaging, apparent diffusion coefficient analysis, diffusion tensor or kurtosis imaging, intravoxel incoherent motion, and other microstructural modeling approaches also allow treatment response assessment; more robust data are required to validate these alone or when applied to post-processing methodologies. Conclusion: Considerable progress has been made in the development of these monitoring biomarkers. Many techniques are in their infancy, whereas others have generated a larger body of evidence for clinical application.
RESUMO
As microscopic tumour infiltration of glioblastomas is not visible on conventional magnetic resonance (MR) imaging, an isotropic expansion of 1-2 cm around the visible tumour is applied to define the clinical target volume for radiotherapy. An opportunity to visualize microscopic infiltration arises with advanced MR imaging. In this review, various advanced MR biomarkers are explored that could improve target volume delineation for radiotherapy of glioblastomas. Various physiological processes in glioblastomas can be visualized with different advanced MR techniques. Combining maps of oxygen metabolism (CMRO2), relative cerebral blood volume (rCBV), vessel size imaging (VSI), and apparent diffusion coefficient (ADC) or amide proton transfer (APT) can provide early information on tumour infiltration and high-risk regions of future recurrence. Oxygen consumption is increased 6 months prior to tumour progression being visible on conventional MR imaging. However, presence of the Warburg effect, marking a switch from an infiltrative to a proliferative phenotype, could result in CMRO2 to appear unaltered in high-risk regions. Including information on biomarkers representing angiogenesis (rCBV and VSI) and hypercellularity (ADC) or protein concentration (APT) can omit misinterpretation due to the Warburg effect. Future research should evaluate these biomarkers in radiotherapy planning to explore the potential of advanced MR techniques to personalize target volume delineation with the aim to improve local tumour control and/or reduce radiation-induced toxicity.