Diagnostic yield of simultaneous dynamic contrast-enhanced magnetic resonance perfusion measurements and [18F]FET PET in patients with suspected recurrent anaplastic astrocytoma and glioblastoma.

PURPOSE: Both amino acid positron emission tomography (PET) and magnetic resonance imaging (MRI) blood volume (BV) measurements are used in suspected recurrent high-grade gliomas. We compared the separate and combined diagnostic yield of simultaneously acquired dynamic contrast-enhanced (DCE) perfusion MRI and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET in patients with anaplastic astrocytoma and glioblastoma following standard therapy. METHODS: A total of 76 lesions in 60 hybrid [18F]FET PET/MRI scans with DCE MRI from patients with suspected recurrence of anaplastic astrocytoma and glioblastoma were included retrospectively. BV was measured from DCE MRI employing a 2-compartment exchange model (2CXM). Diagnostic performances of maximal tumour-to-background [18F]FET uptake (TBRmax), maximal BV (BVmax) and normalised BVmax (nBVmax) were determined by ROC analysis using 6-month histopathological (n = 28) or clinical/radiographical follow-up (n = 48) as reference. Sensitivity and specificity at optimal cut-offs were determined separately for enhancing and non-enhancing lesions. RESULTS: In progressive lesions, all BV and [18F]FET metrics were higher than in non-progressive lesions. ROC analyses showed higher overall ROC AUCs for TBRmax than both BVmax and nBVmax in both lesion-wise (all lesions, p = 0.04) and in patient-wise analysis (p < 0.01). Combining TBRmax with BV metrics did not increase ROC AUC. Lesion-wise positive fraction/sensitivity/specificity at optimal cut-offs were 55%/91%/84% for TBRmax, 45%/77%/84% for BVmax and 59%/84%/72% for nBVmax. Combining TBRmax and best-performing BV cut-offs yielded lesion-wise sensitivity/specificity of 75/97%. The fraction of progressive lesions was 11% in concordant negative lesions, 33% in lesions only BV positive, 64% in lesions only [18F]FET positive and 97% in concordant positive lesions. CONCLUSION: The overall diagnostic accuracy of DCE BV imaging is good, but lower than that of [18F]FET PET. Adding DCE BV imaging did not improve the overall diagnostic accuracy of [18F]FET PET, but may improve specificity and allow better lesion-wise risk stratification than [18F]FET PET alone.

High-Grade Glioma Treatment Response Monitoring Biomarkers: A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 1: Perfusion and Diffusion Techniques.

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.

Deep-learning-based attenuation correction in dynamic [15O]H2O studies using PET/MRI in healthy volunteers.

Quantitative [15O]H2O positron emission tomography (PET) is the accepted reference method for regional cerebral blood flow (rCBF) quantification. To perform reliable quantitative [15O]H2O-PET studies in PET/MRI scanners, MRI-based attenuation-correction (MRAC) is required. Our aim was to compare two MRAC methods (RESOLUTE and DeepUTE) based on ultrashort echo-time with computed tomography-based reference standard AC (CTAC) in dynamic and static [15O]H2O-PET. We compared rCBF from quantitative perfusion maps and activity concentration distribution from static images between AC methods in 25 resting [15O]H2O-PET scans from 14 healthy men at whole-brain, regions of interest and voxel-wise levels. Average whole-brain CBF was 39.9 ± 6.0, 39.0 ± 5.8 and 40.0 ± 5.6 ml/100 g/min for CTAC, RESOLUTE and DeepUTE corrected studies respectively. RESOLUTE underestimated whole-brain CBF by 2.1 ± 1.50% and rCBF in all regions of interest (range -2.4%- -1%) compared to CTAC. DeepUTE showed significant rCBF overestimation only in the occipital lobe (0.6 ± 1.1%). Both MRAC methods showed excellent correlation on rCBF and activity concentration with CTAC, with slopes of linear regression lines between 0.97 and 1.01 and R2 over 0.99. In conclusion, RESOLUTE and DeepUTE provide AC information comparable to CTAC in dynamic [15O]H2O-PET but RESOLUTE is associated with a small but systematic underestimation.

Diagnostic accuracy and clinical impact of [18F]FET PET in childhood CNS tumors.

BACKGROUND: Central nervous system (CNS) tumors cause the highest death rates among childhood cancers, and survivors frequently have severe late effects. Magnetic resonance imaging (MRI) is the imaging modality of choice, but its specificity can be challenged by treatment-induced signal changes. In adults, O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) PET can assist in interpreting MRI findings. We assessed the clinical impact and diagnostic accuracy of adding [18F]FET PET to MRI in children with CNS tumors. METHODS: A total of 169 [18F]FET PET scans were performed in 97 prospectively and consecutively included patients with known or suspected childhood CNS tumors. Scans were performed at primary diagnosis, before or after treatment, or at relapse. RESULTS: Adding [18F]FET PET to MRI impacted clinical management in 8% [95% confidence interval (CI): 4%-13%] of all scans (n = 151) and in 33% [CI: 17%-53%] of scans deemed clinically indicated due to difficult decision making on MRI alone (n = 30). Using pathology or follow-up as reference standard, the addition of [18F]FET PET increased specificity (1.00 [0.82-1.00] vs 0.48 [0.30-0.70], P = .0001) and accuracy (0.91 [CI: 0.87-0.96] vs 0.81 [CI: 0.75-0.89], P = .04) in 83 treated lesions and accuracy in 58 untreated lesions (0.96 [CI: 0.91-1.00] vs 0.90 [CI: 0.82-0.92], P < .001). Further, in a subset of patients (n = 15) [18F]FET uptake correlated positively with genomic proliferation index. CONCLUSIONS: The addition of [18F]FET PET to MRI helped discriminate tumor from non-tumor lesions in the largest consecutive cohort of pediatric CNS tumor patients presented to date.

Regional and interindividual relationships between cerebral perfusion and oxygen metabolism.

Quantitative measurements of resting cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) show large between-subject and regional variability, but the relationships between CBF and CMRO2 measurements regionally and globally are not fully established. Here, we investigated the between-subject and regional associations between CBF and CMRO2 measures with independent and quantitative PET techniques. We included resting CBF and CMRO2 measurements from 50 healthy volunteers (aged 22-81 yr), and calculated the regional and global values of oxygen delivery (Do2) and oxygen extraction fraction (OEF). Linear mixed-model analysis showed that CBF and CMRO2 measurements were closely associated regionally, but no significant between-subject association could be demonstrated, even when adjusting for arterial Pco2 and hemoglobin concentration. The analysis also showed regional differences of OEF, reflecting variable relationship between Do2 and CMRO2, resulting in lower estimates of OEF in thalami, brainstem, and mesial temporal cortices and higher estimates of OEF in occipital cortex. In the present study, we demonstrated no between-subject association of quantitative measurements of CBF and CMRO2 in healthy subjects. Thus, quantitative measurements of CBF did not reflect the underlying between-subject variability of oxygen metabolism measures, mainly because of large interindividual OEF variability not accounted for by Pco2 and hemoglobin concentration.NEW & NOTEWORTHY Using quantitative PET-measurements in healthy human subjects, we confirmed a regional association of CBF and CMRO2, but did not find an association of these values across subjects. This suggests that subjects have an individual coupling between perfusion and metabolism and shows that absolute perfusion measurements does not serve as a surrogate measure of individual measures of oxygen metabolism. The analysis further showed smaller, but significant regional differences of oxygen extraction fraction at rest.

Validation of kinetic modeling of [15O]H2O PET using an image derived input function on hybrid PET/MRI.

In present study we aimed to validate the use of image-derived input functions (IDIF) in the kinetic modeling of cerebral blood flow (CBF) measured by [15O]H2O PET by comparing with the accepted reference standard arterial input function (AIF). Additional comparisons were made to mean cohort AIF and CBF values acquired by methodologically independent phase-contrast mapping (PCM) MRI. Using hybrid PET/MRI an IDIF was generated by measuring the radiotracer concentration in the internal carotid arteries and correcting for partial volume effects using the intravascular volume measured from MRI-angiograms. Seven patients with carotid steno-occlusive disease and twelve healthy controls were examined at rest, after administration of acetazolamide, and, in the control group, during hyperventilation. Agreement between the techniques was examined by linear regression and Bland-Altman analysis. Global CBF values modeled using IDIF correlated with values from AIF across perfusion states in both patients (p<10-6, R2=0.82, 95% limits of agreement (LoA)=[-11.3-9.9] ml/100 g/min) and controls (p<10-6, R2=0.87, 95% LoA=[-17.1-13.7] ml/100 g/min). The reproducibility of gCBF using IDIF was identical to AIF (15.8%). Values from IDIF and AIF had equally good correlation to measurements by PCM MRI, R2=0.86 and R2=0.84, (p<10-6), respectively. Mean cohort AIF performed substantially worse than individual IDIFs (p<10-6, R2=0.63, LoA=[-12.8-25.3] ml/100 g/min). In the patient group, use of IDIF provided similar reactivity maps compared to AIF. In conclusion, global CBF values modeled using IDIF correlated with values modeled by AIF and similar perfusion deficits could be established in a patient group.

High-Grade Glioma Treatment Response Monitoring Biomarkers: A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 2: Spectroscopy, Chemical Exchange Saturation, Multiparametric Imaging, and Radiomics.

Objective: To summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and to highlight the latest bench-to-bedside developments. Methods: The current evidence regarding the potential for monitoring biomarkers was reviewed and individual modalities of metabolism and/or chemical composition imaging discussed. Perfusion, permeability, and microstructure imaging were similarly analyzed in Part 1 of this two-part review article and are valuable reading as background to this article. We appraise the clinic readiness of all the individual modalities and consider methodologies involving machine learning (radiomics) and the combination of MRI approaches (multiparametric imaging). Results: The biochemical composition of high-grade gliomas is markedly different from healthy brain tissue. Magnetic resonance spectroscopy allows the simultaneous acquisition of an array of metabolic alterations, with choline-based ratios appearing to be consistently discriminatory in treatment response assessment, although challenges remain despite this being a mature technique. Promising directions relate to ultra-high field strengths, 2-hydroxyglutarate analysis, and the use of non-proton nuclei. Labile protons on endogenous proteins can be selectively targeted with chemical exchange saturation transfer to give high resolution images. The body of evidence for clinical application of amide proton transfer imaging has been building for a decade, but more evidence is required to confirm chemical exchange saturation transfer use as a monitoring biomarker. Multiparametric methodologies, including the incorporation of nuclear medicine techniques, combine probes measuring different tumor properties. Although potentially synergistic, the limitations of each individual modality also can be compounded, particularly in the absence of standardization. Machine learning requires large datasets with high-quality annotation; there is currently low-level evidence for monitoring biomarker clinical application. Conclusion: Advanced MRI techniques show huge promise in treatment response assessment. The clinical readiness analysis highlights that most monitoring biomarkers require standardized international consensus guidelines, with more facilitation regarding technique implementation and reporting in the clinic.

Effect of blood glucose and body weight on image quality in brain [18F]FDG PET imaging.

OBJECTIVES: The aims of the present study were to assess the influence of mild to moderate hyperglycaemia and body weight on brain 2-[F]fluoro-2-deoxy-D-glucose ([F]FDG) PET, and to what extent a simple algorithm for maintaining count density may compensate for these effects. METHODS: We prospectively included 63 patients undergoing routine brain [F]FDG PET. Scan time and injected activity were adjusted in patients with hyperglycaemia or increased body weight. Measures of perceived image quality, image noise and image contrast were obtained in both standard scans and intervention scans. RESULTS: Elevated blood glucose and increased body weight were associated with reduced count density and increased image noise that in turn were associated with lower scores of perceived image quality. The proposed simple algorithm effectively maintained the image noise level and improved perceived image quality across the full range of elevated blood glucose values and body weights, although the effect of intervention on perceived image quality was attenuated by lower image contrast in patients with moderate hyperglycaemia. In patients with increased body weight or blood glucose, the fraction of scans with poor image quality decreased from 9/29 to 2/29 (P = 0.04) and the fraction with good image quality increased from 7/29 to 20/29 (P = 0.001) when applying the proposed algorithm. CONCLUSIONS: Increasing blood glucose and body weight are associated with increased image noise in standard imaging conditions. Improving count density by prolonging scan time and increasing injected activity significantly improves image quality in hyperglycaemic patients, although the image contrast remains reduced in patients with most pronounced hyperglycaemia.

Quantifying the Financial Savings of Motion Correction in Brain MRI: A Model-Based Estimate of the Costs Arising From Patient Head Motion and Potential Savings From Implementation of Motion Correction.

BACKGROUND: Patient head motion is a major concern in clinical brain MRI, as it reduces the diagnostic image quality and may increase examination time and cost. PURPOSE: To investigate the prevalence of MR images with significant motion artifacts on a given clinical scanner and to estimate the potential financial cost savings of applying motion correction to clinical brain MRI examinations. STUDY TYPE: Retrospective. SUBJECTS: In all, 173 patients undergoing a PET/MRI dementia protocol and 55 pediatric patients undergoing a PET/MRI brain tumor protocol. The total scan time of the two protocols were 17 and 40 minutes, respectively. FIELD STRENGTH/SEQUENCES: 3 T, Siemens mMR Biograph, MPRAGE, DWI, T1 and T2 -weighted FLAIR, T2 -weighted 2D-FLASH, T2 -weighted TSE. ASSESSMENT: A retrospective review of image sequences from a given clinical MRI scanner was conducted to investigate the prevalence of motion-corrupted images. The review was performed by three radiologists with different levels of experience using a three-step semiquantitative scale to classify the quality of the images. A total of 1013 sequences distributed on 228 MRI examinations were reviewed. The potential cost savings of motion correction were estimated by a cost estimation for our country with assumptions. STATISTICAL TEST: The cost estimation was conducted with a 20% lower and upper bound on the model assumptions to include the uncertainty of the assumptions. RESULTS: 7.9% of the sequences had motion artifacts that decreased the interpretability, while 2.0% of the sequences had motion artifacts causing the images to be nondiagnostic. The estimated annual cost to the clinic/hospital due to patient head motion per scanner was $45,066 without pediatric examinations and $364,242 with pediatric examinations. DATA CONCLUSION: The prevalence of a motion-corrupted image was found in 2.0% of the reviewed sequences. Based on the model, repayment periods are presented as a function of the price for applying motion correction and its performance. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 6 J. Magn. Reson. Imaging 2020;52:731-738.

Comparison of simultaneous arterial spin labeling MRI and 15O-H2O PET measurements of regional cerebral blood flow in rest and altered perfusion states.

Arterial spin labelling (ASL) is a non-invasive magnetic resonance imaging (MRI) technique that may provide fully quantitative regional cerebral blood flow (rCBF) images. However, before its application in clinical routine, ASL needs to be validated against the clinical gold standard, 15O-H2O positron emission tomography (PET). We aimed to compare the two techniques by performing simultaneous quantitative ASL-MRI and 15O-H2O-PET examinations in a hybrid PET/MRI scanner. Duplicate rCBF measurements were performed in healthy young subjects (n = 14) in rest, during hyperventilation, and after acetazolamide (post-ACZ), yielding 63 combined PET/MRI datasets in total. Average global CBF by ASL-MRI and 15O-H2O-PET was not significantly different in any state (40.0 ± 6.5 and 40.6 ± 4.1 mL/100 g/min, respectively in rest, 24.5 ± 5.1 and 23.4 ± 4.8 mL/100 g/min, respectively, during hyperventilation, and 59.1 ± 10.4 and 64.7 ± 10.0 mL/100 g/min, respectively, post-ACZ). Overall, strong correlation between the two methods was found across all states (slope = 1.01, R2 = 0.82), while the correlations within individual states and of reactivity measures were weaker, in particular in rest (R2 = 0.05, p = 0.03). Regional distribution was similar, although ASL yielded higher perfusion and absolute reactivity in highly vascularized areas. In conclusion, ASL-MRI and 15O-H2O-PET measurements of rCBF are highly correlated across different perfusion states, but with variable correlation within and between hemodynamic states, and systematic differences in regional distribution.

Markerless motion tracking and correction for PET, MRI, and simultaneous PET/MRI.

OBJECTIVE: We demonstrate and evaluate the first markerless motion tracker compatible with PET, MRI, and simultaneous PET/MRI systems for motion correction (MC) of brain imaging. METHODS: PET and MRI compatibility is achieved by careful positioning of in-bore vision extenders and by placing all electronic components out-of-bore. The motion tracker is demonstrated in a clinical setup during a pediatric PET/MRI study including 94 pediatric patient scans. PET MC is presented for two of these scans using a customized version of the Multiple Acquisition Frame method. Prospective MC of MRI acquisition of two healthy subjects is demonstrated using a motion-aware MRI sequence. Real-time motion estimates are accompanied with a tracking validity parameter to improve tracking reliability. RESULTS: For both modalities, MC shows that motion induced artifacts are noticeably reduced and that motion estimates are sufficiently accurate to capture motion ranging from small respiratory motion to large intentional motion. In the PET/MRI study, a time-activity curve analysis shows image improvements for a patient performing head movements corresponding to a tumor motion of ±5-10 mm with a 19% maximal difference in standardized uptake value before and after MC. CONCLUSION: The first markerless motion tracker is successfully demonstrated for prospective MC in MRI and MC in PET with good tracking validity. SIGNIFICANCE: As simultaneous PET/MRI systems have become available for clinical use, an increasing demand for accurate motion tracking and MC in PET/MRI scans has emerged. The presented markerless motion tracker facilitate this demand.

Phase contrast mapping MRI measurements of global cerebral blood flow across different perfusion states - A direct comparison with 15O-H2O positron emission tomography using a hybrid PET/MR system.

Phase-contrast mapping (PCM) magnetic resonance imaging (MRI) provides easy-access non-invasive quantification of global cerebral blood flow (gCBF) but its accuracy in altered perfusion states is not established. We aimed to compare paired PCM MRI and 15O-H2O positron emission tomography (PET) measurements of gCBF in different perfusion states in a single scanning session. Duplicate combined gCBF PCM-MRI and 15O-H2O PET measurements were performed in the resting condition, during hyperventilation and after acetazolamide administration (post-ACZ) using a 3T hybrid PET/MR system. A total of 62 paired gCBF measurements were acquired in 14 healthy young male volunteers. Average gCBF in resting state measured by PCM-MRI and 15O-H2O PET were 58.5 ± 10.7 and 38.6 ± 5.7 mL/100 g/min, respectively, during hyperventilation 33 ± 8.6 and 24.7 ± 5.8 mL/100 g/min, respectively, and post-ACZ 89.6 ± 27.1 and 57.3 ± 9.6 mL/100 g/min, respectively. On average, gCBF measured by PCM-MRI was 49% higher compared to 15O-H2O PET. A strong correlation between the two methods across all states was observed (R2 = 0.72, p < 0.001). Bland-Altman analysis suggested a perfusion dependent relative bias resulting in higher relative difference at higher CBF values. In conclusion, measurements of gCBF by PCM-MRI in healthy volunteers show a strong correlation with 15O-H2O PET, but are associated with a large and non-linear perfusion-dependent difference.

Interindividual and regional relationship between cerebral blood flow and glucose metabolism in the resting brain.

Studies of the resting brain measurements of cerebral blood flow (CBF) show large interindividual and regional variability, but the metabolic basis of this variability is not fully established. The aim of the present study was to reassess regional and interindividual relationships between cerebral perfusion and glucose metabolism in the resting brain. Regional quantitative measurements of CBF and cerebral metabolic rate of glucose (CMRglc) were obtained in 24 healthy young men using dynamic [15O]H2O and [18F]fluorodeoxyglucose positron emission tomography (PET). Magnetic resonance imaging measurements of global oxygen extraction fraction (gOEF) and metabolic rate of oxygen ([Formula: see text]) were obtained by combined susceptometry-based sagittal sinus oximetry and phase contrast mapping. No significant interindividual associations between global CBF, global CMRglc, and [Formula: see text] were observed. Linear mixed-model analysis showed a highly significant association of CBF with CMRglc regionally. Compared with neocortex significantly higher CBF values than explained by CMRglc were demonstrated in infratentorial structures, thalami, and mesial temporal cortex, and lower values were found in the striatum and cerebral white matter. The present study shows that absolute quantitative global CBF measurements appear not to be a valid surrogate measure of global cerebral glucose or oxygen consumption, and further demonstrates regionally variable relationship between perfusion and glucose metabolism in the resting brain that could suggest regional differences in energy substrate metabolism. NEW & NOTEWORTHY Using method-independent techniques the study cannot confirm direct interindividual correlations of absolute global values of perfusion with oxygen or glucose metabolism in the resting brain, and absolute global perfusion measurements appear not to be valid surrogate measures of cerebral metabolism. The ratio of both perfusion and oxygen delivery to glucose metabolism varies regionally, also when accounting for known methodological regional bias in quantification of glucose metabolism.

Early treatment response evaluation using FET PET compared to MRI in glioblastoma patients at first progression treated with bevacizumab plus lomustine.

BACKGROUND: The goal of this prospective study was to compare the value of both conventional MRI and O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET for response evaluation in glioblastoma patients treated with bevacizumab plus lomustine (BEV/LOM) at first progression. METHODS: After chemoradiation with concomitant and adjuvant temozolomide, 21 IDH wild-type glioblastoma patients at first progression (age range, 33-75 years; MGMT promoter unmethylated, 81%) were treated with BEV/LOM. Contrast-enhanced MRI and FET-PET scans were performed at baseline and after 8-10 weeks. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios. Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the post-progression overall survival (OS) ≤/>9 months as the reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning OS using uni- and multivariate survival estimates. RESULTS: Early treatment response as assessed by RANO criteria was not predictive for an OS>9 months (P = 0.203), whereas relative reductions of all FET-PET parameters significantly predicted an OS>9 months (P < 0.05). The absolute MTV at follow-up enabled the most significant OS prediction (sensitivity, 85%; specificity, 88%; P = 0.001). Patients with an absolute MTV below 5 ml at follow-up survived significantly longer (12 vs. 6 months, P < 0.001), whereas early responders defined by RANO criteria lived only insignificantly longer (9 vs. 6 months; P = 0.072). The absolute MTV at follow-up remained significant in the multivariate survival analysis (P = 0.006). CONCLUSIONS: FET-PET appears to be useful for identifying responders to BEV/LOM early after treatment initiation.

Components of day-to-day variability of cerebral perfusion measurements - Analysis of phase contrast mapping magnetic resonance imaging measurements in healthy volunteers.

PURPOSE: The aim of the study was to investigate the components of day-to-day variability of repeated phase contrast mapping (PCM) magnetic resonance imaging measurements of global cerebral blood flow (gCBF). MATERIALS AND METHODS: Two dataset were analyzed. In Dataset 1 duplicated PCM measurements of total brain flow were performed in 11 healthy young volunteers on two separate days applying a strictly standardized setup. For comparison PCM measurements obtained from a previously published study (Dataset 2) were analyzed in order to assess long-term variability in an aged population in a less strictly controlled setup. Global CBF was calculated by normalizing total brain flow to brain volume. On each day measurements of hemoglobin, caffeine and glucose were obtained. Linear mixed models were applied to estimate coefficients of variation (CV) of total (CVt), between-subject (CVb), within-subject day-to-day (CVw), and intra-session residual variability (CVr). RESULTS: In Dataset 1 CVt, CVb, CVw and CVr were estimated to be 11%, 9.4%, 4% and 4.2%, respectively, and to 8.8%, 7.2%, 2.7% and 4.3%, respectively, when adjusting for hemoglobin and plasma caffeine. In Dataset 2 CVt, CVb and CVw were estimated to be 25.4%, 19.2%, and 15.0%, respectively, and decreased to 16.6%, 8.2% and 12.5%, respectively, when adjusting for the same covariates. DISCUSSION: Our results suggest that short-term day-to-day variability of gCBF is relatively low compared to between-subject variability when studied in standardized conditions, whereas long-term variability in an aged population appears to be much larger when studied in less a standardized setup. The results further showed that from 20% to 35% of the total variability in gCBF can be attributed to the effects of hemoglobin and caffeine.

Clinical PET/MRI in neurooncology: opportunities and challenges from a single-institution perspective.

PURPOSE: Magnetic resonance imaging (MRI) plays a key role in neurooncology, i.e., for diagnosis, treatment evaluation and detection of recurrence. However, standard MRI cannot always separate malignant tissue from other pathologies or treatment-induced changes. Advanced MRI techniques such as diffusion-weighted imaging, perfusion imaging and spectroscopy show promising results in discriminating malignant from benign lesions. Further, supplemental imaging with amino acid positron emission tomography (PET) has been shown to increase accuracy significantly and is used routinely at an increasing number of sites. Several centers are now implementing hybrid PET/MRI systems allowing for multiparametric imaging, combining conventional MRI with advanced MRI and amino acid PET imaging. Neurooncology is an obvious focus area for PET/MR imaging. METHODS: Based on the literature and our experience from more than 300 PET/MRI examinations of brain tumors with 18F-fluoro-ethyl-tyrosine, the clinical use of PET/MRI in adult and pediatric neurooncology is critically reviewed. RESULTS: Although the results are increasingly promising, the added value and range of indications for multiparametric imaging with PET/MRI are yet to be established. Robust solutions to overcome the number of issues when using a PET/MRI scanner are being developed, which is promising for a more routine use in the future. CONCLUSIONS: In a clinical setting, a PET/MRI scan may increase accuracy in discriminating recurrence from treatment changes, although sequential same-day imaging on separate systems will often constitute a reliable and cost-effective alternative. Pediatric patients who require general anesthesia will benefit the most from simultaneous PET and MR imaging.

Clinical PET/MR Imaging in Dementia and Neuro-Oncology.

The introduction of hybrid PET/MRI systems allows simultaneous multimodality image acquisition of high technical quality. This technique is well suited for the brain, and particularly in dementia and neuro-oncology. In routine use combinations of well-established MRI sequences and PET tracers provide the most optimal and clinically valuable protocols. For dementia the [18F]-fluorodeoxyglucose (FDG) has merit with a simultaneous four sequence MRI protocol of 20 min supported by supplementary statistical reading tools and quantitative measurements of the hippocampal volume. Clinical PET/MRI using [18F]-fluoro-ethyl-tyrosine (FET) also abide to the expectations of the adaptive and versatile diagnostic tool necessary in neuro-oncology covering both simple 20 min protocols for routine treatment surveillance and complicated 90 min brain and spinal cord protocols in pediatric neuro-oncology under general anesthesia. The clinical value of adding advanced MRI sequences in multiparametric imaging setting, however, is still undocumented.

Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [(18)F]-fluoroethyltyrosine (FET) PET/MRI: feasibility, agreement and initial experience.

PURPOSE: Both [(18)F]-fluoroethyltyrosine (FET) PET and blood volume (BV) MRI supplement routine T1-weighted contrast-enhanced MRI in gliomas, but whether the two modalities provide identical or complementary information is unresolved. The aims of the study were to investigate the feasibility of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET. METHODS: A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens mMR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial congruence in the tumour volumes determined by FET PET, BV MRI and contrast-enhanced MRI. RESULTS: FET volume and TBRmax were higher in BV-positive than in BV-negative scans, and both VOLBV and rBVmax were higher in FET-positive than in FET-negative scans. TBRmax and rBVmax were positively correlated (R (2) = 0.59, p < 0.001). FET and BV positivity were in agreement in only 26 of the 32 patients and in 42 of 63 lesions, and spatial congruence in the tumour volumes as assessed by the Dice coefficients was generally poor with median Dice coefficients exceeding 0.1 in less than half the patients positive on at least one modality for any pair of modalities. In 56 % of the patients susceptibility artefacts in DSC BV maps overlapped the tumour on MRI. CONCLUSION: The study demonstrated that although tumour volumes determined by BV MRI and FET PET were quantitatively correlated, their spatial congruence in a mixed population of treated glioma patients was generally poor, and the modalities did not provide the same information in this population of patients. Combined imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials.

Motion correction in simultaneous PET/MR brain imaging using sparsely sampled MR navigators: a clinically feasible tool.

BACKGROUND: We present a study performing motion correction (MC) of PET using MR navigators sampled between other protocolled MR sequences during simultaneous PET/MR brain scanning with the purpose of evaluating its clinical feasibility and the potential improvement of image quality. FINDINGS: Twenty-nine human subjects had a 30-min [(11)C]-PiB PET scan with simultaneous MR including 3D navigators sampled at six time points, which were used to correct the PET image for rigid head motion. Five subjects with motion greater than 4 mm were reconstructed into six frames (one for each navigator) which were averaged to one image after MC. The average maximum motion magnitude observed was 3.9 ± 2.4 mm (1 to 11 mm). Visual evaluation by a nuclear medicine physician of the five subjects' motion corrected rated three of the five images blurred before motion correction, while no images were rated blurred after. The image quality was scored on a scale of 1-5, 5 being best. The score changed from an average of 3.4 before motion correction to 4.0 after. There was no correlation between maximum motion magnitude and rating. Quantitative SUVr scoring did not change markedly with motion correction. CONCLUSIONS: Sparsely sampled navigators can be used for characterization and correction of head motion. A slight, overall decrease in blurring and an increase in image quality with MC was found, but without impact on clinical interpretation. In future studies with noteworthy motion artifacts, our method is an important and simple-to-use tool to have available for motion correction.